daniele. lungren, attorney general craig c. thompson ... · craig c. thompson supervising deputy...

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1 2 3 4 5 6 7 8 9 0 : 1 11 12 13 14 1 lt , l, 1 1 2 .., ... .., ... ~ () 1' , ' ·· i - L.J.. W- O I _J <C 0::: 1..W z L.&.J (_!:) >- ' I z C , ..... . ~--· .. DANIELE. LUNGREN, Attorney General of the State of California RODERICK E. WALSTON Chief Assistant Attorney General THEODORA BERGER Assistant Attorney General CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys General 2101 Webster Street, 12th Floor Oakland, CA 94612-3049 Telephone: (510) 286-3892 Anomeys for the People SUPERIOR COURT OF THE STATE OF CALIFORNIA FOR THE CITY AND COUNTY OF SAN FRANCISCO PEOPLE OF THE ST ATE OF CALIFORNIA ex rel. DANIEL E. LUNGREN, Attorney General of the State of California, Plaintiffs, V. WARNER-LAMBERT CO.; SMITHKLINE BEECHAM CORP.; AMERICAN HOME PRODUCTS CORP.; SOURCE NATURAL, INC.; SCHERING-PLOUGH HEALTH CARE PRODUCTS, INC.; PHARMAVITE CORP.; GENERAL NUTRITION CORP.; PERRIGO CO.; TWIN LABORATORIES, INC. and DOES 1-200 Defendants . ) ) ) ) ) ) No. 984503 STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON - ) ) ) ) ) ) ) ) ) - 24 ,.:; ' 2t .-,- STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 1.

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Page 1: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON Supervising Deputy Attorney General

EDWARD G WEIL SUSAN S FIERING (State Bar No 121621)

Deputy Attorneys General 2101 Webster Street 12th Floor Oakland CA 94612-3049 Telephone (510) 286-3892

Anomeys for the People

SUPERIOR COURT OF THE STATE OF CALIFORNIA

FOR THE CITY AND COUNTY OF SAN FRANCISCO

PEOPLE OF THE ST A TE OF CALIFORNIA ex rel DANIEL E LUNGREN Attorney General of the State of California

Plaintiffs V

WARNER-LAMBERT CO SMITHKLINE BEECHAM CORP AMERICAN HOME PRODUCTS CORP SOURCE NATURAL INC SCHERING-PLOUGH HEALTH CARE PRODUCTS INC PHARMAVITE CORP GENERAL NUTRITION CORP PERRIGO CO TWIN LABORATORIES INC and DOES

1-200

Defendants

) )) ) ) )

No 984503

STIPULATION FOR ENTRY OFCONSENT JUDGMENT AND ORDER THEREON

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STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 1

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) Plaintiff the People of the State of California ex rel Daniel E Lungren (People)

and defendant Bayer Corporation (Bayer) herein enter into this Stipulation for Entry of

Consent Judgment (hereinafter Consent Judgment) as follows

1 Introduction

11 On February 6 1997 the People filed a Complaint for Civil Penalties and

Injunctive Relief (Complaint) in the Superior Court of the State of California City and

County of San Francisco against certain defendants On June 16 1997 the People served

Bayer as Doe Defendant Number 5

1 2 Bayer is a company that employs more than ten persons and offers for sale

within the State of California one or more of the following calcium-containing products

(hereinafter Calcium Products) which are intended to be ingested by human beings (a)

products containing primarily calcium that are intended to provide all or a major portion of

the recommended daily allowance of calcium (hereinafter Calcium Supplements) (b)

antacid products containing calcium (hereinafter Antacids) and (c) dietary supplements as

defined in the federal Dietary Supplements Health and Education Act Public Law no 103shy

417 108 Stat 4325 (1994) 21 USC sect 321(ff) containing calcium other than Calcium

Supplements or Antacids (hereinafter Multiple VitaminsMinerals)

1 3 The Peoples Complaint alleges that Bayer through the sale of Calcium Products

to consumers in California violated provisions of the Safe Drinking Water and Toxic

Enforcement Act of 1986 Health and Safety Code sections 252495 et seq (Proposition

65 ) and Business and Professions Code sections 17200 et seq (Unfair Competition Act)

by knowingly exposing persons to lead a chemical known to the State of California to cause

reproductive toxicity without first providing a clear and reasonable warning to such

individuals

14 For purposes of this Consent Judgment only the parties stipulate that this Court

has jurisdiction over the allegations of violations contained in the Complaint and personal

jurisdiction over Bayer as to the acts alleged in the Complaint that venue is proper in the

STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 2

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1 City and County of San Francisco and that this Court has jurisdiction to enter this Consent

2 Judgment

1 5 The parties enter into this Consent Judgment pursuant to a settlement of certain

disputed claims between the parties as alleged in the Complaint for the purpose of avoiding

prolonged and costly litigation between the parties hereto By execution of this Consent

Judgment Bayer does not admit any facts or conclusions of law suggesting or demonstrating

any violations of Proposition 65 the Unfair Competition Act or any other statutory common

law or equitable requirements relating to Calcium Products Nothing in this Consent

Judgment shall be construed as an admission by Bayer of any fact issue of law or violation

of law nor shall compliance with the Consent Judgment constitute or be construed as an

admission by Bayer of any fact issue of law or violation of law Nothing in this Consent

Judgment shall prejudice waive or impair any right remedy or defense Bayer may have in

this or any other or future legal proceedings However this paragraph shall not diminish or

otherwise affect the obligations responsibilities and duties of Bayer under this Consent

Judgment

16 On July 25 1997 this Court entered a stipulated Permanent Injunction

( Permanent Injunction) between the People and Bayer A copy of that document is

anached hereto as Exhibit A The terms of the Permanent Injunction are incorporated into

this Consent Judgment as if fully set forth herein

2 Provisions Concerning Multiple VitaminsMinerals

21 Bayer has provided information to the People concerning its current and past

Multiple VitaminsMinerals A list of those Multiple VitaminsMinerals is attached hereto as

Exhibit B Among the information provided to the People are lead test results from 1993

and 1997 for the Multiple VitaminsMinerals Bayer has also provided information

concerning quality control measures it has taken and will continue to take to insure that its

products are in compliance with Proposition 65

22 Bayer represents that the test results and other information presented to the

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STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 3

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People are true and correct and that the 1997 tests were performed using the protocol

attached as Exhibit A to the Permanent Injunction incorporated herein

23 Based on Bayers representations on the Peoples own test data and on a

review of the test data presented by Bayer the People have determined that Bayers present

products listed in Exhibit B hereto are currently in compliance with Proposition 65 and that

no further injunctive relief is warranted at this time

3 Settlement Payments

31 Within thirty (30) days of approval of this Consent Judgment as full final and

complete satisfaction of all claims for civil penalties or restitution for the alleged violations

up to and including the date of entry of this Consent Judgment as set forth in paragraph 9 1

for Calcium Products Bayer shall pay the sum of $250000 to the Public Health Trust a

program of the California Public Health Foundation to be used for research investigation

and public education projects approved by the Attorney General and relating to exposure to

lead in pregnancy andor nutritional factors related to lead exposure among children

Payment shall be made by delivery of certified funds payable to the Public Health Trust

Making these payments shall not be construed as an admisiion by Bayer of any fact issue of

law or violation of law nor shall compliance with the Consent Judgment constitute or be

construed as an admission by Bayer of any fact issue of law or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of approval of this Consent Judgment Bayer shall pay

$2 500 00 as reimbursement for the Peoples costs of inveitigating and prosecuting this

action Payment shall be made by delivery of certified funds in the amount of $125000

payable to the Attorney General of the State of California at 2101 Webster Street 12th

Floor Oakland California 94612-3049 (Attn Susan S Fiering Deputy Attorney General)

and by the delivery of certified funds in the amount of $125000 payable to the

Environmental Health Account Public Health Trust at 2001 Addison Street Ste 210

Berkeley CA 94704 (with a copy to Susan S Fiering Deputy Attorney General 2101

STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 4

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Webster Street 12th Floor Oakland California 94612-3049)

5 Additional Enforcement Actions Continuing Obligations

5 1 By entering into this Consent Judgment the People do not waive any right to

take further enforcement actions on any violations not covered by the Complaint Nothing in

this Consent Judgment shall be construed as diminishing Bayers continuing obligation to

comply with Proposition 65 or the Unfair Competition Act in its future activities

6 Enforcement of Consent Judgment

6 1 The People may by motion or order to show cause before the Superior Court

of San Francisco enforce the terms and conditions contained in this Consent Judgment In

any action brought by the People to enforce this Consent Judgment the People may seek

whatever fines costs penalties or remedies as provided by law for failure to comply with the

Consent Judgment Where said failure to comply constitutes future violations of Proposition

65 or other laws independent of the Consent Judgment andor those alleged in the

Complaint the People are not limited to enforcement of this Consent Judgment but may

seek in another action whatever fines costs penalties or remedies are provided by law for

failure to comply with Proposition 65 or other laws The rights of Bayer to defend itself and

its actions in law or equity shall not be abrogated or reduced in any fashion by the terms of

this paragraph

7 Application of Consent Judgment

71 The Consent Judgment shall apply to be binding upon and inure to the benefit

of the parties their divisions subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 Authority to Stipulate to Consent Judgment

81 Each signatory to this Consent Judgment certifies that he or she is fully

authorized by the party he or she represents to enter into this Consent Judgment on behalf of

the party represented and legally to bind that party

I

STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND

I ORDER THEREON 5

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9 Claims Covered

91 This Consent Judgment is a final and binding resolution between the People

and Bayer of any and all alleged violations of Proposition 65 the Business and Professions

Code Sections 17200 et seq aandor the Consumers Legal Remedies Act Civil Code section

1750 et seq up through the date of entry of this Consent Judgment arising from failure to

warn of exposure to lead from consumption of Bayers Calcium Products or those of any

corporate affiliate that was committed by Bayer or by any entity within its respective chain

of distribution including but not limited to distributors wholesalers and retailers of any of

Bavers Calcium Products

10 Modification

10 1 This Consent Judgment may be modified from time to time by express written

agreement of Bayer and the Attorney General with the approval of the Court or by an order

of this Court

11 Execution in Counterparts

11 1 This Consent Judgment may be executed in counterparts which taken together

shall be deemed to constitute one and the same document

17 12 Entry of Stipulation for Entry of Consent Judgment Required

12 l This Stipulation for Entry of Consent Judgment shall be null and void and be

without any force or effect unless entered by the Court in this matter If the Stipulation for

Entry of Consent Judgment is not entered by the Court the execution of this Stipulation for

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STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 6

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1 Entry of Consent Judgment by Bayer shall not be construed as an admission- by Bayer of any

fact issue of law or violation of law

IT IS SO STIPULATED

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4 Dated 1-k98I I

1998 DANIEL E LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

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i3 BA YER CORPORATION

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ll~-~By BRUCE KLAFTER Esq Attorneys for Bayer Corporation

IT IS SO ORDERED - 1- middot I L i - L

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LUCY ltELLY McCABEPre~lding Judge

JUDGE SUPERIOR COURT CITY AND COUNTY OF SAN FRANCISCO

STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 7

EXHIBIT A

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 1

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON Supervising Deputy Attorney General

EDWARD G WEIL SUSAN S FIERING (State Bar No 121621)

Deputy Attorneys General 2101 Webster Street 12th Floor Oakland CA 94612-3049 Telephone (510) 286-3892

Attorneys for the People

SUPERIOR COURT OF THE STATE OF CALIFORNIA

FOR THE CITY AND COUNTY OF SAN FRANCISCO

PEOPLE OF THE STATE OF CALIFORNIA ex rel DANIELE LUNGREN Attorney)General of the State of California)

Plaintiffs V

WARNER-LAMBERT CO SMITHKLINE BEECHAM CORP AMERICAN HOME PRODUCTS CORP SOURCE NATURAL INC SCHERING-PLOUGH HEALTH CARE PRODUCTS INC PHARMAVITE CORP GENERAL NUTRITION CORP PERRIGO CO TWIN LABORATORIES INC and DOES 1-200

II Defendants i

No 984503

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND FOR PAYMENT OF SETTLEMENT AMOUNT AND ORDER THEREON

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Plaintiff the People of the State of California (People)

and defendants Bayer Corporation Johnson amp JohnsonMerck

Consumer Pharmaceuticals Nutrilite a Division of Amway

Corporation and Consac (hereinafter collectively Settling

Defendants) herein enter into this Stipulation for Entry of

Permanent Injunction and for Payment of Settlement Amount

(hereinafter Permanent Injunction) as follows

1 Introduction

11 On February 6 1997 the People of the State of

California ex rel Daniel E Lungren (People) filed a

Complaint for Civil Penalties and Injunctive Relief (Complaint)

in the Superior Court of the State of California City and County

of San Francisco against certain defendants On June 5 1997

the People served the Settling Defendants as Does No 5 through 8

respectively

12 Settling Defendants are companies that employ more

than ten persons and offer for sale within the State of

California one or more of the following calcium-containing

products (hereinafter Calcium Products) which are intended to

be ingested by human beings (a) products containing primarily

calcium that are intended to provide all or a major portion of

the recommended daily allowance of calcium (hereinafter Calcium

Supplements) (b) antacid products containing calcium

(hereinafter Antacids) and (c) dietary supplements as defined

in the federal Dietary Supplements Health and Education Act

Public Law no 103-417 108 Stat 4325 (1994) 21 USC sect

321(ff) containing calcium other than Calcium Supplements or

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION

II AND PAYMENT OF SETTLEMENT AMOUNT 2

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Antacids (hereinafter Multiple VitaminsMinerals)

Notwitthstanding any form of packaging of two or more different

alcium Products together the requirements of this Permanent

Injunction shall apply separately to each such different Calcium

froduct The term calcium as used in this Permanent Injunction

means elemental calcium when referring to an amount of calcium

and means any form or salt of calcium when referring to calcium

as an ingredient (active or inactive) in a Calcium Product For purposes of this Permanent Injunction the date of shipment

shall be the date on which the Calcium Product first enters the

stream of commerce except that where a Settling Defendant is

both a manufacturer and a retailer of the Calcium Product date

cf shipment shall mean the date on which a Calcium Product is

transferred from the manufacturing segment of the Settling

Defendants business

13 The Peoples Complaint alleges that Settling

Defendants through the sale of Calcium Products to consumers in

California violated provisions of the Safe Drinking Water and

Toxic Enforcement Act of 1986 Health and Safety Code

sections 252495 et seq (Proposition 65) and Business and

Professions Code sections 1 7200 et seq (Unfair Competition

Act) by knowingly exposing persons to lEiad a chemical known to

the State of California to cause reproductive toxicity without

first providing a clear and reasonable warning to such

25 individuals

14 For purposes of this Permanent Injunction only the

parties stipulate that this Court has jurisdiction over the

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 3

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allegations of violations contained in the Complaint and personal

jurisdiction over the Settling Defendants as to the acts alleged

in the Complaint that venue is proper in the City and County of

San Francisco and that this Court has jurisdiction to enter this

Permanent Injunction

15 The parties enter into this Permanent Injunction

pursuant to a settlement of certain disputed claims between the

parties as alleged in the Complaint for the purpose of avoiding

prolonged and costly litigation between the parties hereto By

execution of this Permanent Injunction Settling Defendants

individually and collectively do not admit any facts or

conclusions of law suggesting or demonstrating any violations of

Proposition 65 the Unfair Competition Act or any other

statutory common law or equitable requirements relating to

Calcium Products Nothing in this Permanent Injunction shall be

construed as an admission by Settling Defendants of any fact

issue of law or violation of law nor shall compliance with the

Permanent Injunction constitute or be construed as an admission

by such Settling Defendants of any fact issue of law or

violation of law Nothing in this Permarnmt Injunction shall

prejudice waive or impair any right remedy or defense such

Settling Defendants may have in this or any other or future legal

proceedings However this paragraph shall not diminish or otherwise affect the obligations responsibilities and duties of

such Settling Defendants individually or collectively under

ttis Permanent Injunction

2 Injunctive Relief - Warning Program

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 4 bull

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21 Where required herein clear and reasonable warning

that use of Calcium Products exposes persons to lead a chemical

known to the State of California to cause birth defects or other

reproductive harm shall be provided by a Settling Defendant in

the manner provided in this Permanent Injunction

22 A Settling Defendant shall provide a warning pursuant

to paragraph 2 5 for each Calcium Product whose date of shipment

is on or after July 1 1997 unless the Settling Defendant can

show pursuant to paragraph 210 and the testing protocol set

forth in Exhibit A attached to this Permanent Injunction that

the Calcium Product causes a total daily exposure to lead of 05

micrograms or less based on the amount of the Calcium Product

supplying a thousand (1000) milligrams of elemental calcium

II excluding any naturally occurring lead in the Calcium Product as

set forth in paragraph 23 below For those Calcium Products

where the recommended or maximum daily dose supplies more than

1500 milligrams of calcium a Settling Defendant shall provide a

I warning unless the Settling Defendant can show pursuant to

paragraph 210 and the testing protocol set forth in attached

i Exhibit A that the recommended daily dose of the Calcium Product

causes a total daily exposure to lead equal to or less than that

set forth in paragraph 24 below

23 A Settling Defendant shall be entitled to exclude from

the calculation of the daily lead exposure caused by a Calcium

Product the amount of lead per 1000 milligrams of calcium as set

forth in Table 23 of this paragraph 23 Compliance with this

Permanent Injunction is established and no warning is required

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 5

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under Proposition 65 where the lead exposure caused by an amount

of the Calcium Product supplying 1000 milligrams of calcium does

d not exceed the sum of (a) 05 micrograms of lead per thousand

milligrams of elemental calcium and (b) the amount of lead

excluded on the date of shipment as naturally occurring

pursuant to Table 23 of this paragraph 23 For purposes of

this Permanent Injunction Table 23 of this paragraph 23 sets

forth the amount of lead per 1000 milligrams of elemental calcium

which shall be deemed to be naturally occurring at the lowest

level currently feasible pursuant to Section 12501 of Title 22

cf the California Code of Regulations (CCR) The amounts of

lead and dates set forth in Table 23 shall apply as of the date

of shipment of the Calcium Product

TABLE 2 3

DATE NATURALLY OCCURRING AMOUNT OF LEAD PER 1000 MILLIGRAMS OF CALCIUM

July 1 1997 35 micrograms

April 1 1999 10 microgram

24 Even if no warning is required by paragraphs 22 and

23 above in the event that the recommended daily dose of any

Calcium Product as specified on the label or in any other

package material exceeds 1500 milligrams a Settling Defendant

shall provide a warning pursuant to Propcsition 65 if the total

daily lead exposure from the Calcium Product based on the

recommended daily dose exceeds 150 of the level that would

require a warning pursuant to paragraphs 22 and 23 (based on a

an amount of the Calcium Product supplying 1000 milligrams of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 6

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calcium) above as of the date of shipment of the Calcium Product

For antacids that do not have a recommended daily dose for

purposes of this Permanent Injunction the term recommended

daily dose shall mean two-thirds of the maximum daily dose as

set forth on the label or in any other package material

25 For a Calcium Product that does not meet the standards

set forth in paragraphs 2 2 through 2 4 above a Settling

Defendant shall at the point of manufacture prior to shipment

to California or prior to distribution within California (1)

affix to or print on the Calcium Product container cap label or

unit package or (2) display at the point of sale of the Calcium

Product the following warning (the language in brackets in the

warning below is optional)

WARNING This product contains [lead] a chemical known [to the State of California] to cause birth defects or other reproductive harm

26 The warning required by paragraph 25 above shall be

prominently affixed to printed on or displayed proximately to

the point-of-sale of each Calcium Product with such

conspicuousness as compared with other words statements

designs or devices on the labeling as to render it likely to be

read and understood by an ordinary individual under customary

conditions of purchase or use If the warning is displayed on

the product container or labeling the warning shall be at least

the same size as the largest of any other health or safety

warnings on the product container or labeling and the word

warning 11 shall be in all capital letters and in bold print If

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printed on the labeling itself the warning shall be contained in

the same section of the labeling that states other safety

warnings concerning the use of the product The Attorney General

agrees to review any labeling or point of sale signs proposed to

be used under this section and advise the Settling Defendant as

to whether he believes such labeling or point of sale signs

comply with this section The requirement for product labeling

set forth herein is imposed pursuant to the terms of this

Permanent Injunction and is recognized by the parties as not

being the exclusive method of providing a warning under

Proposition 65 and its implementing regulations for the Calcium

Products

27 In the event that the Attorney General determines that

the naturally occurring levels set forth in Table 23 of

paragraph 23 above are higher than the lowest level currently

feasible as stated in 22 CCR section 12501 (a) (4) he shall have

the right to seek a modification of the Permanent Injunction to

reflect the alleged lowest level currently feasible of

naturally occurring lead in the Calcium Products Prior to

seeking such modification the Attorney General shall provide

written notice to the Settling Defendants that he intends to seek

the modification The parties shall have ninety (90) days in

which to confer with the Attorney General concerning the

modification If one or more of the Settling Defendants and the

Attorney General are unable to agree on a modification to the

Permanent Injunction the Attorney General may file a motion with

the court seeking a modification of the Permanent Injunction

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

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In any motion by the Attorney General seeking such a

modification the burden of producing evidence shall be initially

upon the Attorney General to demonstrate a prima facie case that

the modification sought by the Attorney General is the lowest

level currently feasible The Settling Defendants who do not

agree to such modification retain the ultimate burden of proving

that the modification sought by the Attorney General is lower

than the lowest level currently feasible The parties hereby

agree that the Permanent Injunction should be modified to reflect

any agreement of the parties or any deterrrination by the Court

concerning what is the lowest level currently feasible for lead

in Calcium Products

28 In the event that Settling Defendants individually or

coilectively determine that the naturally occurring levels set

forth in Table 23 of paragraph 23 above are lower than the

lowest level currently feasible as stated in 22 CCR section

1250l(a) (4) such Settling Defendants shall have the right to

seek modification of the Permanent Injunction to reflect the

alleged lowest level currently feasible Prior to seeking such

modification such Settling Defendants shall provide written

notice to the Attorney General that they intend to seek the

modification The parties shall have ninety (90) days in which

to confer concerning the modification If the parties are unable

to agree on a modification to the Permanent Injunction such

Settling Defendants may file a motion with the Court seeking a

modification of the Permanent Injunction In any motion by

Settling Defendants seeking such modification the burden of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 9

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27

producing evidence and of proof shall be on such Settling

Defendants to prove that the modification sought by the Settling

Defendants is the lowest level currently feasible The parties

hereby agree that the Permanent Injunction should be modified to

reflect any agreement of the parties or any determination by the

Court concerning what is the lowest level currently feasible

I for lead in Calcium Products

29 The term feasible as used in paragraphs 27 and 28

above includes but is not limited to a consideration of the

following factors availability and reliabilityof a supply of

low-lead calcium that meets the requirememts set forth in

paragraphs 22 23 and 24 above cost of low-lead calcium and

resulting increase in manufacturers prices resulting from the

use of the low-lead calcium performance characteristics of lowshy

lead calcium and of the resulting Calcium Product including but

middot not limited to formulation performance safety efficacy and

stability Nothing in this Permanent Injunction shall be

interpreted to require the Settling Defendants to use any calcium

material as an ingredient in a Calcium Product that would render

i their Calcium Product unlawful under state or federal law as

measured by existing andor future applicable California and

federal food and drug laws and regulations Nothing in this

Permanent Injunction shall be interpreted to preclude a Settling

Defendant from advocating for purposes of paragraphs 27 andor

28 that any proposed modification requiring a change in the type

of raw calcium source material as an ingredient in a Calcium

Product is not feasible as defined herein Nothing in this

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 10

ii

I

II I II

I

ii bullI

1

2

middot

4

c

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- ii

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Permanent Injunction shall be interpreted to preclude the People

from advocating for purposes of paragraphs 2 7 andor 2 8 that

any proposed modification requiring a change in the type of raw

Calcium source material as an ingredient in a calcium product is

feasible as defined herein

9

1 c

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13

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21

22

23

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210 Each Settling Defendant shall maintain records

sufficient to establish its compliance with this Permanent

Injunction for a period of four years following the date of

shipment of any Calcium Product into California Such documents

shall be sufficient in detail to establish compliance with the

Protocol set forth in the attached Exhibit A Upon reasonable written notice from the Attorney Generals Office a Settling

Defendant must produce to the Attorney General within ten (10)

tusiness days of the receipt of the Attorney Generals notice

the documents required to be maintained according to this

paragraph To the extent that such documents contain information

which the Settling Defendant maintains is confidential

proprietary andor in the nature of a trade secret (or in fact a

trade secret) and upon written notice as to the asserted

confidential nature of this information by the Settling

Defendant the Attorney General agrees not to disclose this

information to third parties (though the Attorney General may

disclose this information to its attorneys and employees

including professional consultants provided that these persons

also agree to maintain the confidentiality of the information in

these documents) In addition any Settling Defendant may

designate as confidential trade secret information as that term

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 11

1

2

3

4

5

6

7

8

9

~c

2

l~

1 bull C _

~

20

21

22

23

24

25

26

27

is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

11

l

2

3

4

~

6

7

8

9

1

11

12

J3

l 4

17

l 3

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shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

21

l

2

3

4

5

6

7

8

9

1G

11

2

3

14

JI

~7

s

~9

20

i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

22

23

24 [l

25 II I

26

2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

II al - Ii

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

l

2

3

4

E

7

8 1

9 1

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21

22 1

Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

8

l

1 )

1L

l L

l

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8

bull =

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22

23

24

25

26

27

i I

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for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

I

IIi

2 1111

31

4 I

) II 11

1~ 11 ii

7 fl

s II 1

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for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

middotJC-~ J 14~ LJ - ---lt__

Its S-~ LIL~~ Pr-ltt-S1J~L

Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

2

~ li

4

5 middot

E

E

C

the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

8

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---

-

6

Its

Dated CONSAC

By

Its

APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

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Dated

7

8

Dated 7997

l ) AP PROVED AS TO FORM

Dated

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~ IS SO ORDERED

By

Its

NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

L c

2 l

2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

C

6

7

8

g

0

11

12

15

16

1 7

8

19

21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

lbull9116I 21 11Jl

I

Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

l-litl~ 4ll lUl

Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

l HI l 6l Vl l I IJ2

Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

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Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 2: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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) Plaintiff the People of the State of California ex rel Daniel E Lungren (People)

and defendant Bayer Corporation (Bayer) herein enter into this Stipulation for Entry of

Consent Judgment (hereinafter Consent Judgment) as follows

1 Introduction

11 On February 6 1997 the People filed a Complaint for Civil Penalties and

Injunctive Relief (Complaint) in the Superior Court of the State of California City and

County of San Francisco against certain defendants On June 16 1997 the People served

Bayer as Doe Defendant Number 5

1 2 Bayer is a company that employs more than ten persons and offers for sale

within the State of California one or more of the following calcium-containing products

(hereinafter Calcium Products) which are intended to be ingested by human beings (a)

products containing primarily calcium that are intended to provide all or a major portion of

the recommended daily allowance of calcium (hereinafter Calcium Supplements) (b)

antacid products containing calcium (hereinafter Antacids) and (c) dietary supplements as

defined in the federal Dietary Supplements Health and Education Act Public Law no 103shy

417 108 Stat 4325 (1994) 21 USC sect 321(ff) containing calcium other than Calcium

Supplements or Antacids (hereinafter Multiple VitaminsMinerals)

1 3 The Peoples Complaint alleges that Bayer through the sale of Calcium Products

to consumers in California violated provisions of the Safe Drinking Water and Toxic

Enforcement Act of 1986 Health and Safety Code sections 252495 et seq (Proposition

65 ) and Business and Professions Code sections 17200 et seq (Unfair Competition Act)

by knowingly exposing persons to lead a chemical known to the State of California to cause

reproductive toxicity without first providing a clear and reasonable warning to such

individuals

14 For purposes of this Consent Judgment only the parties stipulate that this Court

has jurisdiction over the allegations of violations contained in the Complaint and personal

jurisdiction over Bayer as to the acts alleged in the Complaint that venue is proper in the

STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 2

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1 City and County of San Francisco and that this Court has jurisdiction to enter this Consent

2 Judgment

1 5 The parties enter into this Consent Judgment pursuant to a settlement of certain

disputed claims between the parties as alleged in the Complaint for the purpose of avoiding

prolonged and costly litigation between the parties hereto By execution of this Consent

Judgment Bayer does not admit any facts or conclusions of law suggesting or demonstrating

any violations of Proposition 65 the Unfair Competition Act or any other statutory common

law or equitable requirements relating to Calcium Products Nothing in this Consent

Judgment shall be construed as an admission by Bayer of any fact issue of law or violation

of law nor shall compliance with the Consent Judgment constitute or be construed as an

admission by Bayer of any fact issue of law or violation of law Nothing in this Consent

Judgment shall prejudice waive or impair any right remedy or defense Bayer may have in

this or any other or future legal proceedings However this paragraph shall not diminish or

otherwise affect the obligations responsibilities and duties of Bayer under this Consent

Judgment

16 On July 25 1997 this Court entered a stipulated Permanent Injunction

( Permanent Injunction) between the People and Bayer A copy of that document is

anached hereto as Exhibit A The terms of the Permanent Injunction are incorporated into

this Consent Judgment as if fully set forth herein

2 Provisions Concerning Multiple VitaminsMinerals

21 Bayer has provided information to the People concerning its current and past

Multiple VitaminsMinerals A list of those Multiple VitaminsMinerals is attached hereto as

Exhibit B Among the information provided to the People are lead test results from 1993

and 1997 for the Multiple VitaminsMinerals Bayer has also provided information

concerning quality control measures it has taken and will continue to take to insure that its

products are in compliance with Proposition 65

22 Bayer represents that the test results and other information presented to the

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STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 3

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People are true and correct and that the 1997 tests were performed using the protocol

attached as Exhibit A to the Permanent Injunction incorporated herein

23 Based on Bayers representations on the Peoples own test data and on a

review of the test data presented by Bayer the People have determined that Bayers present

products listed in Exhibit B hereto are currently in compliance with Proposition 65 and that

no further injunctive relief is warranted at this time

3 Settlement Payments

31 Within thirty (30) days of approval of this Consent Judgment as full final and

complete satisfaction of all claims for civil penalties or restitution for the alleged violations

up to and including the date of entry of this Consent Judgment as set forth in paragraph 9 1

for Calcium Products Bayer shall pay the sum of $250000 to the Public Health Trust a

program of the California Public Health Foundation to be used for research investigation

and public education projects approved by the Attorney General and relating to exposure to

lead in pregnancy andor nutritional factors related to lead exposure among children

Payment shall be made by delivery of certified funds payable to the Public Health Trust

Making these payments shall not be construed as an admisiion by Bayer of any fact issue of

law or violation of law nor shall compliance with the Consent Judgment constitute or be

construed as an admission by Bayer of any fact issue of law or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of approval of this Consent Judgment Bayer shall pay

$2 500 00 as reimbursement for the Peoples costs of inveitigating and prosecuting this

action Payment shall be made by delivery of certified funds in the amount of $125000

payable to the Attorney General of the State of California at 2101 Webster Street 12th

Floor Oakland California 94612-3049 (Attn Susan S Fiering Deputy Attorney General)

and by the delivery of certified funds in the amount of $125000 payable to the

Environmental Health Account Public Health Trust at 2001 Addison Street Ste 210

Berkeley CA 94704 (with a copy to Susan S Fiering Deputy Attorney General 2101

STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 4

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Webster Street 12th Floor Oakland California 94612-3049)

5 Additional Enforcement Actions Continuing Obligations

5 1 By entering into this Consent Judgment the People do not waive any right to

take further enforcement actions on any violations not covered by the Complaint Nothing in

this Consent Judgment shall be construed as diminishing Bayers continuing obligation to

comply with Proposition 65 or the Unfair Competition Act in its future activities

6 Enforcement of Consent Judgment

6 1 The People may by motion or order to show cause before the Superior Court

of San Francisco enforce the terms and conditions contained in this Consent Judgment In

any action brought by the People to enforce this Consent Judgment the People may seek

whatever fines costs penalties or remedies as provided by law for failure to comply with the

Consent Judgment Where said failure to comply constitutes future violations of Proposition

65 or other laws independent of the Consent Judgment andor those alleged in the

Complaint the People are not limited to enforcement of this Consent Judgment but may

seek in another action whatever fines costs penalties or remedies are provided by law for

failure to comply with Proposition 65 or other laws The rights of Bayer to defend itself and

its actions in law or equity shall not be abrogated or reduced in any fashion by the terms of

this paragraph

7 Application of Consent Judgment

71 The Consent Judgment shall apply to be binding upon and inure to the benefit

of the parties their divisions subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 Authority to Stipulate to Consent Judgment

81 Each signatory to this Consent Judgment certifies that he or she is fully

authorized by the party he or she represents to enter into this Consent Judgment on behalf of

the party represented and legally to bind that party

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STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND

I ORDER THEREON 5

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9 Claims Covered

91 This Consent Judgment is a final and binding resolution between the People

and Bayer of any and all alleged violations of Proposition 65 the Business and Professions

Code Sections 17200 et seq aandor the Consumers Legal Remedies Act Civil Code section

1750 et seq up through the date of entry of this Consent Judgment arising from failure to

warn of exposure to lead from consumption of Bayers Calcium Products or those of any

corporate affiliate that was committed by Bayer or by any entity within its respective chain

of distribution including but not limited to distributors wholesalers and retailers of any of

Bavers Calcium Products

10 Modification

10 1 This Consent Judgment may be modified from time to time by express written

agreement of Bayer and the Attorney General with the approval of the Court or by an order

of this Court

11 Execution in Counterparts

11 1 This Consent Judgment may be executed in counterparts which taken together

shall be deemed to constitute one and the same document

17 12 Entry of Stipulation for Entry of Consent Judgment Required

12 l This Stipulation for Entry of Consent Judgment shall be null and void and be

without any force or effect unless entered by the Court in this matter If the Stipulation for

Entry of Consent Judgment is not entered by the Court the execution of this Stipulation for

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STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 6

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1 Entry of Consent Judgment by Bayer shall not be construed as an admission- by Bayer of any

fact issue of law or violation of law

IT IS SO STIPULATED

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4 Dated 1-k98I I

1998 DANIEL E LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

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i3 BA YER CORPORATION

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Dep Attorneys General

By

DatedJ-eeuro-shy 4 l7itf

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T)t~ 5vmiddot Ko1pon

Vice PresidentIts

APPROVED AS TO FORM

Dated -qf4 ORRICK HERRINGTON amp SUTCLIFFE

ll~-~By BRUCE KLAFTER Esq Attorneys for Bayer Corporation

IT IS SO ORDERED - 1- middot I L i - L

Dated

)

LUCY ltELLY McCABEPre~lding Judge

JUDGE SUPERIOR COURT CITY AND COUNTY OF SAN FRANCISCO

STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 7

EXHIBIT A

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 1

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON Supervising Deputy Attorney General

EDWARD G WEIL SUSAN S FIERING (State Bar No 121621)

Deputy Attorneys General 2101 Webster Street 12th Floor Oakland CA 94612-3049 Telephone (510) 286-3892

Attorneys for the People

SUPERIOR COURT OF THE STATE OF CALIFORNIA

FOR THE CITY AND COUNTY OF SAN FRANCISCO

PEOPLE OF THE STATE OF CALIFORNIA ex rel DANIELE LUNGREN Attorney)General of the State of California)

Plaintiffs V

WARNER-LAMBERT CO SMITHKLINE BEECHAM CORP AMERICAN HOME PRODUCTS CORP SOURCE NATURAL INC SCHERING-PLOUGH HEALTH CARE PRODUCTS INC PHARMAVITE CORP GENERAL NUTRITION CORP PERRIGO CO TWIN LABORATORIES INC and DOES 1-200

II Defendants i

No 984503

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND FOR PAYMENT OF SETTLEMENT AMOUNT AND ORDER THEREON

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Plaintiff the People of the State of California (People)

and defendants Bayer Corporation Johnson amp JohnsonMerck

Consumer Pharmaceuticals Nutrilite a Division of Amway

Corporation and Consac (hereinafter collectively Settling

Defendants) herein enter into this Stipulation for Entry of

Permanent Injunction and for Payment of Settlement Amount

(hereinafter Permanent Injunction) as follows

1 Introduction

11 On February 6 1997 the People of the State of

California ex rel Daniel E Lungren (People) filed a

Complaint for Civil Penalties and Injunctive Relief (Complaint)

in the Superior Court of the State of California City and County

of San Francisco against certain defendants On June 5 1997

the People served the Settling Defendants as Does No 5 through 8

respectively

12 Settling Defendants are companies that employ more

than ten persons and offer for sale within the State of

California one or more of the following calcium-containing

products (hereinafter Calcium Products) which are intended to

be ingested by human beings (a) products containing primarily

calcium that are intended to provide all or a major portion of

the recommended daily allowance of calcium (hereinafter Calcium

Supplements) (b) antacid products containing calcium

(hereinafter Antacids) and (c) dietary supplements as defined

in the federal Dietary Supplements Health and Education Act

Public Law no 103-417 108 Stat 4325 (1994) 21 USC sect

321(ff) containing calcium other than Calcium Supplements or

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION

II AND PAYMENT OF SETTLEMENT AMOUNT 2

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Antacids (hereinafter Multiple VitaminsMinerals)

Notwitthstanding any form of packaging of two or more different

alcium Products together the requirements of this Permanent

Injunction shall apply separately to each such different Calcium

froduct The term calcium as used in this Permanent Injunction

means elemental calcium when referring to an amount of calcium

and means any form or salt of calcium when referring to calcium

as an ingredient (active or inactive) in a Calcium Product For purposes of this Permanent Injunction the date of shipment

shall be the date on which the Calcium Product first enters the

stream of commerce except that where a Settling Defendant is

both a manufacturer and a retailer of the Calcium Product date

cf shipment shall mean the date on which a Calcium Product is

transferred from the manufacturing segment of the Settling

Defendants business

13 The Peoples Complaint alleges that Settling

Defendants through the sale of Calcium Products to consumers in

California violated provisions of the Safe Drinking Water and

Toxic Enforcement Act of 1986 Health and Safety Code

sections 252495 et seq (Proposition 65) and Business and

Professions Code sections 1 7200 et seq (Unfair Competition

Act) by knowingly exposing persons to lEiad a chemical known to

the State of California to cause reproductive toxicity without

first providing a clear and reasonable warning to such

25 individuals

14 For purposes of this Permanent Injunction only the

parties stipulate that this Court has jurisdiction over the

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 3

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allegations of violations contained in the Complaint and personal

jurisdiction over the Settling Defendants as to the acts alleged

in the Complaint that venue is proper in the City and County of

San Francisco and that this Court has jurisdiction to enter this

Permanent Injunction

15 The parties enter into this Permanent Injunction

pursuant to a settlement of certain disputed claims between the

parties as alleged in the Complaint for the purpose of avoiding

prolonged and costly litigation between the parties hereto By

execution of this Permanent Injunction Settling Defendants

individually and collectively do not admit any facts or

conclusions of law suggesting or demonstrating any violations of

Proposition 65 the Unfair Competition Act or any other

statutory common law or equitable requirements relating to

Calcium Products Nothing in this Permanent Injunction shall be

construed as an admission by Settling Defendants of any fact

issue of law or violation of law nor shall compliance with the

Permanent Injunction constitute or be construed as an admission

by such Settling Defendants of any fact issue of law or

violation of law Nothing in this Permarnmt Injunction shall

prejudice waive or impair any right remedy or defense such

Settling Defendants may have in this or any other or future legal

proceedings However this paragraph shall not diminish or otherwise affect the obligations responsibilities and duties of

such Settling Defendants individually or collectively under

ttis Permanent Injunction

2 Injunctive Relief - Warning Program

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 4 bull

1

2

3

4

S

6

7

8

9

lJ

11

12

13

14

15

16

17

18

19

2 O

21

22

24

25

26

27

21 Where required herein clear and reasonable warning

that use of Calcium Products exposes persons to lead a chemical

known to the State of California to cause birth defects or other

reproductive harm shall be provided by a Settling Defendant in

the manner provided in this Permanent Injunction

22 A Settling Defendant shall provide a warning pursuant

to paragraph 2 5 for each Calcium Product whose date of shipment

is on or after July 1 1997 unless the Settling Defendant can

show pursuant to paragraph 210 and the testing protocol set

forth in Exhibit A attached to this Permanent Injunction that

the Calcium Product causes a total daily exposure to lead of 05

micrograms or less based on the amount of the Calcium Product

supplying a thousand (1000) milligrams of elemental calcium

II excluding any naturally occurring lead in the Calcium Product as

set forth in paragraph 23 below For those Calcium Products

where the recommended or maximum daily dose supplies more than

1500 milligrams of calcium a Settling Defendant shall provide a

I warning unless the Settling Defendant can show pursuant to

paragraph 210 and the testing protocol set forth in attached

i Exhibit A that the recommended daily dose of the Calcium Product

causes a total daily exposure to lead equal to or less than that

set forth in paragraph 24 below

23 A Settling Defendant shall be entitled to exclude from

the calculation of the daily lead exposure caused by a Calcium

Product the amount of lead per 1000 milligrams of calcium as set

forth in Table 23 of this paragraph 23 Compliance with this

Permanent Injunction is established and no warning is required

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 5

1

2

3

4

5

6

7

8

9

10

Jl

12

3

14

1 5

26

under Proposition 65 where the lead exposure caused by an amount

of the Calcium Product supplying 1000 milligrams of calcium does

d not exceed the sum of (a) 05 micrograms of lead per thousand

milligrams of elemental calcium and (b) the amount of lead

excluded on the date of shipment as naturally occurring

pursuant to Table 23 of this paragraph 23 For purposes of

this Permanent Injunction Table 23 of this paragraph 23 sets

forth the amount of lead per 1000 milligrams of elemental calcium

which shall be deemed to be naturally occurring at the lowest

level currently feasible pursuant to Section 12501 of Title 22

cf the California Code of Regulations (CCR) The amounts of

lead and dates set forth in Table 23 shall apply as of the date

of shipment of the Calcium Product

TABLE 2 3

DATE NATURALLY OCCURRING AMOUNT OF LEAD PER 1000 MILLIGRAMS OF CALCIUM

July 1 1997 35 micrograms

April 1 1999 10 microgram

24 Even if no warning is required by paragraphs 22 and

23 above in the event that the recommended daily dose of any

Calcium Product as specified on the label or in any other

package material exceeds 1500 milligrams a Settling Defendant

shall provide a warning pursuant to Propcsition 65 if the total

daily lead exposure from the Calcium Product based on the

recommended daily dose exceeds 150 of the level that would

require a warning pursuant to paragraphs 22 and 23 (based on a

an amount of the Calcium Product supplying 1000 milligrams of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 6

23

27

1

2

3

4

5 J

6

7

8

9

10

11

12

J 8

2 1 1

2 5

27

calcium) above as of the date of shipment of the Calcium Product

For antacids that do not have a recommended daily dose for

purposes of this Permanent Injunction the term recommended

daily dose shall mean two-thirds of the maximum daily dose as

set forth on the label or in any other package material

25 For a Calcium Product that does not meet the standards

set forth in paragraphs 2 2 through 2 4 above a Settling

Defendant shall at the point of manufacture prior to shipment

to California or prior to distribution within California (1)

affix to or print on the Calcium Product container cap label or

unit package or (2) display at the point of sale of the Calcium

Product the following warning (the language in brackets in the

warning below is optional)

WARNING This product contains [lead] a chemical known [to the State of California] to cause birth defects or other reproductive harm

26 The warning required by paragraph 25 above shall be

prominently affixed to printed on or displayed proximately to

the point-of-sale of each Calcium Product with such

conspicuousness as compared with other words statements

designs or devices on the labeling as to render it likely to be

read and understood by an ordinary individual under customary

conditions of purchase or use If the warning is displayed on

the product container or labeling the warning shall be at least

the same size as the largest of any other health or safety

warnings on the product container or labeling and the word

warning 11 shall be in all capital letters and in bold print If

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 7

1

2

3

4

5

6

7

B

9

lO

11

12

14

1 5

19

20

21

22

23

24

25

26

27

printed on the labeling itself the warning shall be contained in

the same section of the labeling that states other safety

warnings concerning the use of the product The Attorney General

agrees to review any labeling or point of sale signs proposed to

be used under this section and advise the Settling Defendant as

to whether he believes such labeling or point of sale signs

comply with this section The requirement for product labeling

set forth herein is imposed pursuant to the terms of this

Permanent Injunction and is recognized by the parties as not

being the exclusive method of providing a warning under

Proposition 65 and its implementing regulations for the Calcium

Products

27 In the event that the Attorney General determines that

the naturally occurring levels set forth in Table 23 of

paragraph 23 above are higher than the lowest level currently

feasible as stated in 22 CCR section 12501 (a) (4) he shall have

the right to seek a modification of the Permanent Injunction to

reflect the alleged lowest level currently feasible of

naturally occurring lead in the Calcium Products Prior to

seeking such modification the Attorney General shall provide

written notice to the Settling Defendants that he intends to seek

the modification The parties shall have ninety (90) days in

which to confer with the Attorney General concerning the

modification If one or more of the Settling Defendants and the

Attorney General are unable to agree on a modification to the

Permanent Injunction the Attorney General may file a motion with

the court seeking a modification of the Permanent Injunction

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

I AMOUNT 8

1

2

3

4

5

6

7

B

9

10

11 1

12

13

14

l

16

17

18

19

2

2

2

23

24

25

26

2-1

In any motion by the Attorney General seeking such a

modification the burden of producing evidence shall be initially

upon the Attorney General to demonstrate a prima facie case that

the modification sought by the Attorney General is the lowest

level currently feasible The Settling Defendants who do not

agree to such modification retain the ultimate burden of proving

that the modification sought by the Attorney General is lower

than the lowest level currently feasible The parties hereby

agree that the Permanent Injunction should be modified to reflect

any agreement of the parties or any deterrrination by the Court

concerning what is the lowest level currently feasible for lead

in Calcium Products

28 In the event that Settling Defendants individually or

coilectively determine that the naturally occurring levels set

forth in Table 23 of paragraph 23 above are lower than the

lowest level currently feasible as stated in 22 CCR section

1250l(a) (4) such Settling Defendants shall have the right to

seek modification of the Permanent Injunction to reflect the

alleged lowest level currently feasible Prior to seeking such

modification such Settling Defendants shall provide written

notice to the Attorney General that they intend to seek the

modification The parties shall have ninety (90) days in which

to confer concerning the modification If the parties are unable

to agree on a modification to the Permanent Injunction such

Settling Defendants may file a motion with the Court seeking a

modification of the Permanent Injunction In any motion by

Settling Defendants seeking such modification the burden of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 9

1

1

2

3 Ii I

4 j

5 i I

6

7

8

9

10

11

12

L~

14

15

16

17

18

L 3

2J

21

22

23

24

25

26

27

producing evidence and of proof shall be on such Settling

Defendants to prove that the modification sought by the Settling

Defendants is the lowest level currently feasible The parties

hereby agree that the Permanent Injunction should be modified to

reflect any agreement of the parties or any determination by the

Court concerning what is the lowest level currently feasible

I for lead in Calcium Products

29 The term feasible as used in paragraphs 27 and 28

above includes but is not limited to a consideration of the

following factors availability and reliabilityof a supply of

low-lead calcium that meets the requirememts set forth in

paragraphs 22 23 and 24 above cost of low-lead calcium and

resulting increase in manufacturers prices resulting from the

use of the low-lead calcium performance characteristics of lowshy

lead calcium and of the resulting Calcium Product including but

middot not limited to formulation performance safety efficacy and

stability Nothing in this Permanent Injunction shall be

interpreted to require the Settling Defendants to use any calcium

material as an ingredient in a Calcium Product that would render

i their Calcium Product unlawful under state or federal law as

measured by existing andor future applicable California and

federal food and drug laws and regulations Nothing in this

Permanent Injunction shall be interpreted to preclude a Settling

Defendant from advocating for purposes of paragraphs 27 andor

28 that any proposed modification requiring a change in the type

of raw calcium source material as an ingredient in a Calcium

Product is not feasible as defined herein Nothing in this

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 10

ii

I

II I II

I

ii bullI

1

2

middot

4

c

E I

- ii

8

Permanent Injunction shall be interpreted to preclude the People

from advocating for purposes of paragraphs 2 7 andor 2 8 that

any proposed modification requiring a change in the type of raw

Calcium source material as an ingredient in a calcium product is

feasible as defined herein

9

1 c

1

I

1

I

IIIII

J~

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1~

18

13

2J

21

22

23

~4

25

26

27

I

II

210 Each Settling Defendant shall maintain records

sufficient to establish its compliance with this Permanent

Injunction for a period of four years following the date of

shipment of any Calcium Product into California Such documents

shall be sufficient in detail to establish compliance with the

Protocol set forth in the attached Exhibit A Upon reasonable written notice from the Attorney Generals Office a Settling

Defendant must produce to the Attorney General within ten (10)

tusiness days of the receipt of the Attorney Generals notice

the documents required to be maintained according to this

paragraph To the extent that such documents contain information

which the Settling Defendant maintains is confidential

proprietary andor in the nature of a trade secret (or in fact a

trade secret) and upon written notice as to the asserted

confidential nature of this information by the Settling

Defendant the Attorney General agrees not to disclose this

information to third parties (though the Attorney General may

disclose this information to its attorneys and employees

including professional consultants provided that these persons

also agree to maintain the confidentiality of the information in

these documents) In addition any Settling Defendant may

designate as confidential trade secret information as that term

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 11

1

2

3

4

5

6

7

8

9

~c

2

l~

1 bull C _

~

20

21

22

23

24

25

26

27

is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

11

l

2

3

4

~

6

7

8

9

1

11

12

J3

l 4

17

l 3

~l

~6

shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

21

l

2

3

4

5

6

7

8

9

1G

11

2

3

14

JI

~7

s

~9

20

i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

22

23

24 [l

25 II I

26

2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

II al - Ii

I

1

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1 I

I

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

l

2

3

4

E

7

8 1

9 1

c I

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21

22 1

Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

8

l

1 )

1L

l L

l

- C

8

bull =

)()

) I

22

23

24

25

26

27

i I

ii

for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

I

IIi

2 1111

31

4 I

) II 11

1~ 11 ii

7 fl

s II 1

g 1 I

l )

for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

middotJC-~ J 14~ LJ - ---lt__

Its S-~ LIL~~ Pr-ltt-S1J~L

Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

2

~ li

4

5 middot

E

E

C

the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

8

_ _

---

-

6

Its

Dated CONSAC

By

Its

APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

3

Dated

7

8

Dated 7997

l ) AP PROVED AS TO FORM

Dated

l -~

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By

Its

NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

L c

2 l

2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

C

6

7

8

g

0

11

12

15

16

1 7

8

19

21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

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22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

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23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

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24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

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252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

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Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

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E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

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C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

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3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

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315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

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preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

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Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 3: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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1 City and County of San Francisco and that this Court has jurisdiction to enter this Consent

2 Judgment

1 5 The parties enter into this Consent Judgment pursuant to a settlement of certain

disputed claims between the parties as alleged in the Complaint for the purpose of avoiding

prolonged and costly litigation between the parties hereto By execution of this Consent

Judgment Bayer does not admit any facts or conclusions of law suggesting or demonstrating

any violations of Proposition 65 the Unfair Competition Act or any other statutory common

law or equitable requirements relating to Calcium Products Nothing in this Consent

Judgment shall be construed as an admission by Bayer of any fact issue of law or violation

of law nor shall compliance with the Consent Judgment constitute or be construed as an

admission by Bayer of any fact issue of law or violation of law Nothing in this Consent

Judgment shall prejudice waive or impair any right remedy or defense Bayer may have in

this or any other or future legal proceedings However this paragraph shall not diminish or

otherwise affect the obligations responsibilities and duties of Bayer under this Consent

Judgment

16 On July 25 1997 this Court entered a stipulated Permanent Injunction

( Permanent Injunction) between the People and Bayer A copy of that document is

anached hereto as Exhibit A The terms of the Permanent Injunction are incorporated into

this Consent Judgment as if fully set forth herein

2 Provisions Concerning Multiple VitaminsMinerals

21 Bayer has provided information to the People concerning its current and past

Multiple VitaminsMinerals A list of those Multiple VitaminsMinerals is attached hereto as

Exhibit B Among the information provided to the People are lead test results from 1993

and 1997 for the Multiple VitaminsMinerals Bayer has also provided information

concerning quality control measures it has taken and will continue to take to insure that its

products are in compliance with Proposition 65

22 Bayer represents that the test results and other information presented to the

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STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 3

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People are true and correct and that the 1997 tests were performed using the protocol

attached as Exhibit A to the Permanent Injunction incorporated herein

23 Based on Bayers representations on the Peoples own test data and on a

review of the test data presented by Bayer the People have determined that Bayers present

products listed in Exhibit B hereto are currently in compliance with Proposition 65 and that

no further injunctive relief is warranted at this time

3 Settlement Payments

31 Within thirty (30) days of approval of this Consent Judgment as full final and

complete satisfaction of all claims for civil penalties or restitution for the alleged violations

up to and including the date of entry of this Consent Judgment as set forth in paragraph 9 1

for Calcium Products Bayer shall pay the sum of $250000 to the Public Health Trust a

program of the California Public Health Foundation to be used for research investigation

and public education projects approved by the Attorney General and relating to exposure to

lead in pregnancy andor nutritional factors related to lead exposure among children

Payment shall be made by delivery of certified funds payable to the Public Health Trust

Making these payments shall not be construed as an admisiion by Bayer of any fact issue of

law or violation of law nor shall compliance with the Consent Judgment constitute or be

construed as an admission by Bayer of any fact issue of law or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of approval of this Consent Judgment Bayer shall pay

$2 500 00 as reimbursement for the Peoples costs of inveitigating and prosecuting this

action Payment shall be made by delivery of certified funds in the amount of $125000

payable to the Attorney General of the State of California at 2101 Webster Street 12th

Floor Oakland California 94612-3049 (Attn Susan S Fiering Deputy Attorney General)

and by the delivery of certified funds in the amount of $125000 payable to the

Environmental Health Account Public Health Trust at 2001 Addison Street Ste 210

Berkeley CA 94704 (with a copy to Susan S Fiering Deputy Attorney General 2101

STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 4

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5 Additional Enforcement Actions Continuing Obligations

5 1 By entering into this Consent Judgment the People do not waive any right to

take further enforcement actions on any violations not covered by the Complaint Nothing in

this Consent Judgment shall be construed as diminishing Bayers continuing obligation to

comply with Proposition 65 or the Unfair Competition Act in its future activities

6 Enforcement of Consent Judgment

6 1 The People may by motion or order to show cause before the Superior Court

of San Francisco enforce the terms and conditions contained in this Consent Judgment In

any action brought by the People to enforce this Consent Judgment the People may seek

whatever fines costs penalties or remedies as provided by law for failure to comply with the

Consent Judgment Where said failure to comply constitutes future violations of Proposition

65 or other laws independent of the Consent Judgment andor those alleged in the

Complaint the People are not limited to enforcement of this Consent Judgment but may

seek in another action whatever fines costs penalties or remedies are provided by law for

failure to comply with Proposition 65 or other laws The rights of Bayer to defend itself and

its actions in law or equity shall not be abrogated or reduced in any fashion by the terms of

this paragraph

7 Application of Consent Judgment

71 The Consent Judgment shall apply to be binding upon and inure to the benefit

of the parties their divisions subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 Authority to Stipulate to Consent Judgment

81 Each signatory to this Consent Judgment certifies that he or she is fully

authorized by the party he or she represents to enter into this Consent Judgment on behalf of

the party represented and legally to bind that party

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STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND

I ORDER THEREON 5

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9 Claims Covered

91 This Consent Judgment is a final and binding resolution between the People

and Bayer of any and all alleged violations of Proposition 65 the Business and Professions

Code Sections 17200 et seq aandor the Consumers Legal Remedies Act Civil Code section

1750 et seq up through the date of entry of this Consent Judgment arising from failure to

warn of exposure to lead from consumption of Bayers Calcium Products or those of any

corporate affiliate that was committed by Bayer or by any entity within its respective chain

of distribution including but not limited to distributors wholesalers and retailers of any of

Bavers Calcium Products

10 Modification

10 1 This Consent Judgment may be modified from time to time by express written

agreement of Bayer and the Attorney General with the approval of the Court or by an order

of this Court

11 Execution in Counterparts

11 1 This Consent Judgment may be executed in counterparts which taken together

shall be deemed to constitute one and the same document

17 12 Entry of Stipulation for Entry of Consent Judgment Required

12 l This Stipulation for Entry of Consent Judgment shall be null and void and be

without any force or effect unless entered by the Court in this matter If the Stipulation for

Entry of Consent Judgment is not entered by the Court the execution of this Stipulation for

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STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 6

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1 Entry of Consent Judgment by Bayer shall not be construed as an admission- by Bayer of any

fact issue of law or violation of law

IT IS SO STIPULATED

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4 Dated 1-k98I I

1998 DANIEL E LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

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i3 BA YER CORPORATION

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Dep Attorneys General

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DatedJ-eeuro-shy 4 l7itf

By

T)t~ 5vmiddot Ko1pon

Vice PresidentIts

APPROVED AS TO FORM

Dated -qf4 ORRICK HERRINGTON amp SUTCLIFFE

ll~-~By BRUCE KLAFTER Esq Attorneys for Bayer Corporation

IT IS SO ORDERED - 1- middot I L i - L

Dated

)

LUCY ltELLY McCABEPre~lding Judge

JUDGE SUPERIOR COURT CITY AND COUNTY OF SAN FRANCISCO

STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 7

EXHIBIT A

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 1

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON Supervising Deputy Attorney General

EDWARD G WEIL SUSAN S FIERING (State Bar No 121621)

Deputy Attorneys General 2101 Webster Street 12th Floor Oakland CA 94612-3049 Telephone (510) 286-3892

Attorneys for the People

SUPERIOR COURT OF THE STATE OF CALIFORNIA

FOR THE CITY AND COUNTY OF SAN FRANCISCO

PEOPLE OF THE STATE OF CALIFORNIA ex rel DANIELE LUNGREN Attorney)General of the State of California)

Plaintiffs V

WARNER-LAMBERT CO SMITHKLINE BEECHAM CORP AMERICAN HOME PRODUCTS CORP SOURCE NATURAL INC SCHERING-PLOUGH HEALTH CARE PRODUCTS INC PHARMAVITE CORP GENERAL NUTRITION CORP PERRIGO CO TWIN LABORATORIES INC and DOES 1-200

II Defendants i

No 984503

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND FOR PAYMENT OF SETTLEMENT AMOUNT AND ORDER THEREON

5

10

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20

25

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23

24

26

27

Plaintiff the People of the State of California (People)

and defendants Bayer Corporation Johnson amp JohnsonMerck

Consumer Pharmaceuticals Nutrilite a Division of Amway

Corporation and Consac (hereinafter collectively Settling

Defendants) herein enter into this Stipulation for Entry of

Permanent Injunction and for Payment of Settlement Amount

(hereinafter Permanent Injunction) as follows

1 Introduction

11 On February 6 1997 the People of the State of

California ex rel Daniel E Lungren (People) filed a

Complaint for Civil Penalties and Injunctive Relief (Complaint)

in the Superior Court of the State of California City and County

of San Francisco against certain defendants On June 5 1997

the People served the Settling Defendants as Does No 5 through 8

respectively

12 Settling Defendants are companies that employ more

than ten persons and offer for sale within the State of

California one or more of the following calcium-containing

products (hereinafter Calcium Products) which are intended to

be ingested by human beings (a) products containing primarily

calcium that are intended to provide all or a major portion of

the recommended daily allowance of calcium (hereinafter Calcium

Supplements) (b) antacid products containing calcium

(hereinafter Antacids) and (c) dietary supplements as defined

in the federal Dietary Supplements Health and Education Act

Public Law no 103-417 108 Stat 4325 (1994) 21 USC sect

321(ff) containing calcium other than Calcium Supplements or

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION

II AND PAYMENT OF SETTLEMENT AMOUNT 2

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Antacids (hereinafter Multiple VitaminsMinerals)

Notwitthstanding any form of packaging of two or more different

alcium Products together the requirements of this Permanent

Injunction shall apply separately to each such different Calcium

froduct The term calcium as used in this Permanent Injunction

means elemental calcium when referring to an amount of calcium

and means any form or salt of calcium when referring to calcium

as an ingredient (active or inactive) in a Calcium Product For purposes of this Permanent Injunction the date of shipment

shall be the date on which the Calcium Product first enters the

stream of commerce except that where a Settling Defendant is

both a manufacturer and a retailer of the Calcium Product date

cf shipment shall mean the date on which a Calcium Product is

transferred from the manufacturing segment of the Settling

Defendants business

13 The Peoples Complaint alleges that Settling

Defendants through the sale of Calcium Products to consumers in

California violated provisions of the Safe Drinking Water and

Toxic Enforcement Act of 1986 Health and Safety Code

sections 252495 et seq (Proposition 65) and Business and

Professions Code sections 1 7200 et seq (Unfair Competition

Act) by knowingly exposing persons to lEiad a chemical known to

the State of California to cause reproductive toxicity without

first providing a clear and reasonable warning to such

25 individuals

14 For purposes of this Permanent Injunction only the

parties stipulate that this Court has jurisdiction over the

26

27

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 3

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allegations of violations contained in the Complaint and personal

jurisdiction over the Settling Defendants as to the acts alleged

in the Complaint that venue is proper in the City and County of

San Francisco and that this Court has jurisdiction to enter this

Permanent Injunction

15 The parties enter into this Permanent Injunction

pursuant to a settlement of certain disputed claims between the

parties as alleged in the Complaint for the purpose of avoiding

prolonged and costly litigation between the parties hereto By

execution of this Permanent Injunction Settling Defendants

individually and collectively do not admit any facts or

conclusions of law suggesting or demonstrating any violations of

Proposition 65 the Unfair Competition Act or any other

statutory common law or equitable requirements relating to

Calcium Products Nothing in this Permanent Injunction shall be

construed as an admission by Settling Defendants of any fact

issue of law or violation of law nor shall compliance with the

Permanent Injunction constitute or be construed as an admission

by such Settling Defendants of any fact issue of law or

violation of law Nothing in this Permarnmt Injunction shall

prejudice waive or impair any right remedy or defense such

Settling Defendants may have in this or any other or future legal

proceedings However this paragraph shall not diminish or otherwise affect the obligations responsibilities and duties of

such Settling Defendants individually or collectively under

ttis Permanent Injunction

2 Injunctive Relief - Warning Program

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 4 bull

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21 Where required herein clear and reasonable warning

that use of Calcium Products exposes persons to lead a chemical

known to the State of California to cause birth defects or other

reproductive harm shall be provided by a Settling Defendant in

the manner provided in this Permanent Injunction

22 A Settling Defendant shall provide a warning pursuant

to paragraph 2 5 for each Calcium Product whose date of shipment

is on or after July 1 1997 unless the Settling Defendant can

show pursuant to paragraph 210 and the testing protocol set

forth in Exhibit A attached to this Permanent Injunction that

the Calcium Product causes a total daily exposure to lead of 05

micrograms or less based on the amount of the Calcium Product

supplying a thousand (1000) milligrams of elemental calcium

II excluding any naturally occurring lead in the Calcium Product as

set forth in paragraph 23 below For those Calcium Products

where the recommended or maximum daily dose supplies more than

1500 milligrams of calcium a Settling Defendant shall provide a

I warning unless the Settling Defendant can show pursuant to

paragraph 210 and the testing protocol set forth in attached

i Exhibit A that the recommended daily dose of the Calcium Product

causes a total daily exposure to lead equal to or less than that

set forth in paragraph 24 below

23 A Settling Defendant shall be entitled to exclude from

the calculation of the daily lead exposure caused by a Calcium

Product the amount of lead per 1000 milligrams of calcium as set

forth in Table 23 of this paragraph 23 Compliance with this

Permanent Injunction is established and no warning is required

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 5

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5

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8

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under Proposition 65 where the lead exposure caused by an amount

of the Calcium Product supplying 1000 milligrams of calcium does

d not exceed the sum of (a) 05 micrograms of lead per thousand

milligrams of elemental calcium and (b) the amount of lead

excluded on the date of shipment as naturally occurring

pursuant to Table 23 of this paragraph 23 For purposes of

this Permanent Injunction Table 23 of this paragraph 23 sets

forth the amount of lead per 1000 milligrams of elemental calcium

which shall be deemed to be naturally occurring at the lowest

level currently feasible pursuant to Section 12501 of Title 22

cf the California Code of Regulations (CCR) The amounts of

lead and dates set forth in Table 23 shall apply as of the date

of shipment of the Calcium Product

TABLE 2 3

DATE NATURALLY OCCURRING AMOUNT OF LEAD PER 1000 MILLIGRAMS OF CALCIUM

July 1 1997 35 micrograms

April 1 1999 10 microgram

24 Even if no warning is required by paragraphs 22 and

23 above in the event that the recommended daily dose of any

Calcium Product as specified on the label or in any other

package material exceeds 1500 milligrams a Settling Defendant

shall provide a warning pursuant to Propcsition 65 if the total

daily lead exposure from the Calcium Product based on the

recommended daily dose exceeds 150 of the level that would

require a warning pursuant to paragraphs 22 and 23 (based on a

an amount of the Calcium Product supplying 1000 milligrams of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 6

23

27

1

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4

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6

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2 1 1

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calcium) above as of the date of shipment of the Calcium Product

For antacids that do not have a recommended daily dose for

purposes of this Permanent Injunction the term recommended

daily dose shall mean two-thirds of the maximum daily dose as

set forth on the label or in any other package material

25 For a Calcium Product that does not meet the standards

set forth in paragraphs 2 2 through 2 4 above a Settling

Defendant shall at the point of manufacture prior to shipment

to California or prior to distribution within California (1)

affix to or print on the Calcium Product container cap label or

unit package or (2) display at the point of sale of the Calcium

Product the following warning (the language in brackets in the

warning below is optional)

WARNING This product contains [lead] a chemical known [to the State of California] to cause birth defects or other reproductive harm

26 The warning required by paragraph 25 above shall be

prominently affixed to printed on or displayed proximately to

the point-of-sale of each Calcium Product with such

conspicuousness as compared with other words statements

designs or devices on the labeling as to render it likely to be

read and understood by an ordinary individual under customary

conditions of purchase or use If the warning is displayed on

the product container or labeling the warning shall be at least

the same size as the largest of any other health or safety

warnings on the product container or labeling and the word

warning 11 shall be in all capital letters and in bold print If

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 7

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printed on the labeling itself the warning shall be contained in

the same section of the labeling that states other safety

warnings concerning the use of the product The Attorney General

agrees to review any labeling or point of sale signs proposed to

be used under this section and advise the Settling Defendant as

to whether he believes such labeling or point of sale signs

comply with this section The requirement for product labeling

set forth herein is imposed pursuant to the terms of this

Permanent Injunction and is recognized by the parties as not

being the exclusive method of providing a warning under

Proposition 65 and its implementing regulations for the Calcium

Products

27 In the event that the Attorney General determines that

the naturally occurring levels set forth in Table 23 of

paragraph 23 above are higher than the lowest level currently

feasible as stated in 22 CCR section 12501 (a) (4) he shall have

the right to seek a modification of the Permanent Injunction to

reflect the alleged lowest level currently feasible of

naturally occurring lead in the Calcium Products Prior to

seeking such modification the Attorney General shall provide

written notice to the Settling Defendants that he intends to seek

the modification The parties shall have ninety (90) days in

which to confer with the Attorney General concerning the

modification If one or more of the Settling Defendants and the

Attorney General are unable to agree on a modification to the

Permanent Injunction the Attorney General may file a motion with

the court seeking a modification of the Permanent Injunction

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

I AMOUNT 8

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2

3

4

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6

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In any motion by the Attorney General seeking such a

modification the burden of producing evidence shall be initially

upon the Attorney General to demonstrate a prima facie case that

the modification sought by the Attorney General is the lowest

level currently feasible The Settling Defendants who do not

agree to such modification retain the ultimate burden of proving

that the modification sought by the Attorney General is lower

than the lowest level currently feasible The parties hereby

agree that the Permanent Injunction should be modified to reflect

any agreement of the parties or any deterrrination by the Court

concerning what is the lowest level currently feasible for lead

in Calcium Products

28 In the event that Settling Defendants individually or

coilectively determine that the naturally occurring levels set

forth in Table 23 of paragraph 23 above are lower than the

lowest level currently feasible as stated in 22 CCR section

1250l(a) (4) such Settling Defendants shall have the right to

seek modification of the Permanent Injunction to reflect the

alleged lowest level currently feasible Prior to seeking such

modification such Settling Defendants shall provide written

notice to the Attorney General that they intend to seek the

modification The parties shall have ninety (90) days in which

to confer concerning the modification If the parties are unable

to agree on a modification to the Permanent Injunction such

Settling Defendants may file a motion with the Court seeking a

modification of the Permanent Injunction In any motion by

Settling Defendants seeking such modification the burden of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 9

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producing evidence and of proof shall be on such Settling

Defendants to prove that the modification sought by the Settling

Defendants is the lowest level currently feasible The parties

hereby agree that the Permanent Injunction should be modified to

reflect any agreement of the parties or any determination by the

Court concerning what is the lowest level currently feasible

I for lead in Calcium Products

29 The term feasible as used in paragraphs 27 and 28

above includes but is not limited to a consideration of the

following factors availability and reliabilityof a supply of

low-lead calcium that meets the requirememts set forth in

paragraphs 22 23 and 24 above cost of low-lead calcium and

resulting increase in manufacturers prices resulting from the

use of the low-lead calcium performance characteristics of lowshy

lead calcium and of the resulting Calcium Product including but

middot not limited to formulation performance safety efficacy and

stability Nothing in this Permanent Injunction shall be

interpreted to require the Settling Defendants to use any calcium

material as an ingredient in a Calcium Product that would render

i their Calcium Product unlawful under state or federal law as

measured by existing andor future applicable California and

federal food and drug laws and regulations Nothing in this

Permanent Injunction shall be interpreted to preclude a Settling

Defendant from advocating for purposes of paragraphs 27 andor

28 that any proposed modification requiring a change in the type

of raw calcium source material as an ingredient in a Calcium

Product is not feasible as defined herein Nothing in this

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 10

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Permanent Injunction shall be interpreted to preclude the People

from advocating for purposes of paragraphs 2 7 andor 2 8 that

any proposed modification requiring a change in the type of raw

Calcium source material as an ingredient in a calcium product is

feasible as defined herein

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210 Each Settling Defendant shall maintain records

sufficient to establish its compliance with this Permanent

Injunction for a period of four years following the date of

shipment of any Calcium Product into California Such documents

shall be sufficient in detail to establish compliance with the

Protocol set forth in the attached Exhibit A Upon reasonable written notice from the Attorney Generals Office a Settling

Defendant must produce to the Attorney General within ten (10)

tusiness days of the receipt of the Attorney Generals notice

the documents required to be maintained according to this

paragraph To the extent that such documents contain information

which the Settling Defendant maintains is confidential

proprietary andor in the nature of a trade secret (or in fact a

trade secret) and upon written notice as to the asserted

confidential nature of this information by the Settling

Defendant the Attorney General agrees not to disclose this

information to third parties (though the Attorney General may

disclose this information to its attorneys and employees

including professional consultants provided that these persons

also agree to maintain the confidentiality of the information in

these documents) In addition any Settling Defendant may

designate as confidential trade secret information as that term

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 11

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is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

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shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

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2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

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Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

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for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

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for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

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Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

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the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

8

_ _

---

-

6

Its

Dated CONSAC

By

Its

APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

3

Dated

7

8

Dated 7997

l ) AP PROVED AS TO FORM

Dated

l -~

~ IS SO ORDERED

By

Its

NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

L c

2 l

2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

C

6

7

8

g

0

11

12

15

16

1 7

8

19

21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

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Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 4: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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People are true and correct and that the 1997 tests were performed using the protocol

attached as Exhibit A to the Permanent Injunction incorporated herein

23 Based on Bayers representations on the Peoples own test data and on a

review of the test data presented by Bayer the People have determined that Bayers present

products listed in Exhibit B hereto are currently in compliance with Proposition 65 and that

no further injunctive relief is warranted at this time

3 Settlement Payments

31 Within thirty (30) days of approval of this Consent Judgment as full final and

complete satisfaction of all claims for civil penalties or restitution for the alleged violations

up to and including the date of entry of this Consent Judgment as set forth in paragraph 9 1

for Calcium Products Bayer shall pay the sum of $250000 to the Public Health Trust a

program of the California Public Health Foundation to be used for research investigation

and public education projects approved by the Attorney General and relating to exposure to

lead in pregnancy andor nutritional factors related to lead exposure among children

Payment shall be made by delivery of certified funds payable to the Public Health Trust

Making these payments shall not be construed as an admisiion by Bayer of any fact issue of

law or violation of law nor shall compliance with the Consent Judgment constitute or be

construed as an admission by Bayer of any fact issue of law or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of approval of this Consent Judgment Bayer shall pay

$2 500 00 as reimbursement for the Peoples costs of inveitigating and prosecuting this

action Payment shall be made by delivery of certified funds in the amount of $125000

payable to the Attorney General of the State of California at 2101 Webster Street 12th

Floor Oakland California 94612-3049 (Attn Susan S Fiering Deputy Attorney General)

and by the delivery of certified funds in the amount of $125000 payable to the

Environmental Health Account Public Health Trust at 2001 Addison Street Ste 210

Berkeley CA 94704 (with a copy to Susan S Fiering Deputy Attorney General 2101

STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 4

1

2

3

4

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8

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1C

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11

13 14

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21

22

23

24

2 5

26

Webster Street 12th Floor Oakland California 94612-3049)

5 Additional Enforcement Actions Continuing Obligations

5 1 By entering into this Consent Judgment the People do not waive any right to

take further enforcement actions on any violations not covered by the Complaint Nothing in

this Consent Judgment shall be construed as diminishing Bayers continuing obligation to

comply with Proposition 65 or the Unfair Competition Act in its future activities

6 Enforcement of Consent Judgment

6 1 The People may by motion or order to show cause before the Superior Court

of San Francisco enforce the terms and conditions contained in this Consent Judgment In

any action brought by the People to enforce this Consent Judgment the People may seek

whatever fines costs penalties or remedies as provided by law for failure to comply with the

Consent Judgment Where said failure to comply constitutes future violations of Proposition

65 or other laws independent of the Consent Judgment andor those alleged in the

Complaint the People are not limited to enforcement of this Consent Judgment but may

seek in another action whatever fines costs penalties or remedies are provided by law for

failure to comply with Proposition 65 or other laws The rights of Bayer to defend itself and

its actions in law or equity shall not be abrogated or reduced in any fashion by the terms of

this paragraph

7 Application of Consent Judgment

71 The Consent Judgment shall apply to be binding upon and inure to the benefit

of the parties their divisions subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 Authority to Stipulate to Consent Judgment

81 Each signatory to this Consent Judgment certifies that he or she is fully

authorized by the party he or she represents to enter into this Consent Judgment on behalf of

the party represented and legally to bind that party

I

STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND

I ORDER THEREON 5

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

9 Claims Covered

91 This Consent Judgment is a final and binding resolution between the People

and Bayer of any and all alleged violations of Proposition 65 the Business and Professions

Code Sections 17200 et seq aandor the Consumers Legal Remedies Act Civil Code section

1750 et seq up through the date of entry of this Consent Judgment arising from failure to

warn of exposure to lead from consumption of Bayers Calcium Products or those of any

corporate affiliate that was committed by Bayer or by any entity within its respective chain

of distribution including but not limited to distributors wholesalers and retailers of any of

Bavers Calcium Products

10 Modification

10 1 This Consent Judgment may be modified from time to time by express written

agreement of Bayer and the Attorney General with the approval of the Court or by an order

of this Court

11 Execution in Counterparts

11 1 This Consent Judgment may be executed in counterparts which taken together

shall be deemed to constitute one and the same document

17 12 Entry of Stipulation for Entry of Consent Judgment Required

12 l This Stipulation for Entry of Consent Judgment shall be null and void and be

without any force or effect unless entered by the Court in this matter If the Stipulation for

Entry of Consent Judgment is not entered by the Court the execution of this Stipulation for

18

19

20

21

23

24

26

27

STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 6

--------

--------------

1 Entry of Consent Judgment by Bayer shall not be construed as an admission- by Bayer of any

fact issue of law or violation of law

IT IS SO STIPULATED

2

3

4 Dated 1-k98I I

1998 DANIEL E LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

5

6

7

8

9

10

11

12

i3 BA YER CORPORATION

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Dep Attorneys General

By

DatedJ-eeuro-shy 4 l7itf

By

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Vice PresidentIts

APPROVED AS TO FORM

Dated -qf4 ORRICK HERRINGTON amp SUTCLIFFE

ll~-~By BRUCE KLAFTER Esq Attorneys for Bayer Corporation

IT IS SO ORDERED - 1- middot I L i - L

Dated

)

LUCY ltELLY McCABEPre~lding Judge

JUDGE SUPERIOR COURT CITY AND COUNTY OF SAN FRANCISCO

STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 7

EXHIBIT A

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 1

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON Supervising Deputy Attorney General

EDWARD G WEIL SUSAN S FIERING (State Bar No 121621)

Deputy Attorneys General 2101 Webster Street 12th Floor Oakland CA 94612-3049 Telephone (510) 286-3892

Attorneys for the People

SUPERIOR COURT OF THE STATE OF CALIFORNIA

FOR THE CITY AND COUNTY OF SAN FRANCISCO

PEOPLE OF THE STATE OF CALIFORNIA ex rel DANIELE LUNGREN Attorney)General of the State of California)

Plaintiffs V

WARNER-LAMBERT CO SMITHKLINE BEECHAM CORP AMERICAN HOME PRODUCTS CORP SOURCE NATURAL INC SCHERING-PLOUGH HEALTH CARE PRODUCTS INC PHARMAVITE CORP GENERAL NUTRITION CORP PERRIGO CO TWIN LABORATORIES INC and DOES 1-200

II Defendants i

No 984503

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND FOR PAYMENT OF SETTLEMENT AMOUNT AND ORDER THEREON

5

10

15

20

25

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12

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21

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23

24

26

27

Plaintiff the People of the State of California (People)

and defendants Bayer Corporation Johnson amp JohnsonMerck

Consumer Pharmaceuticals Nutrilite a Division of Amway

Corporation and Consac (hereinafter collectively Settling

Defendants) herein enter into this Stipulation for Entry of

Permanent Injunction and for Payment of Settlement Amount

(hereinafter Permanent Injunction) as follows

1 Introduction

11 On February 6 1997 the People of the State of

California ex rel Daniel E Lungren (People) filed a

Complaint for Civil Penalties and Injunctive Relief (Complaint)

in the Superior Court of the State of California City and County

of San Francisco against certain defendants On June 5 1997

the People served the Settling Defendants as Does No 5 through 8

respectively

12 Settling Defendants are companies that employ more

than ten persons and offer for sale within the State of

California one or more of the following calcium-containing

products (hereinafter Calcium Products) which are intended to

be ingested by human beings (a) products containing primarily

calcium that are intended to provide all or a major portion of

the recommended daily allowance of calcium (hereinafter Calcium

Supplements) (b) antacid products containing calcium

(hereinafter Antacids) and (c) dietary supplements as defined

in the federal Dietary Supplements Health and Education Act

Public Law no 103-417 108 Stat 4325 (1994) 21 USC sect

321(ff) containing calcium other than Calcium Supplements or

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION

II AND PAYMENT OF SETTLEMENT AMOUNT 2

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2

3

4

5

6 I

7

8 I

9

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14

15

17

18

19

20

21

22

23

24

Antacids (hereinafter Multiple VitaminsMinerals)

Notwitthstanding any form of packaging of two or more different

alcium Products together the requirements of this Permanent

Injunction shall apply separately to each such different Calcium

froduct The term calcium as used in this Permanent Injunction

means elemental calcium when referring to an amount of calcium

and means any form or salt of calcium when referring to calcium

as an ingredient (active or inactive) in a Calcium Product For purposes of this Permanent Injunction the date of shipment

shall be the date on which the Calcium Product first enters the

stream of commerce except that where a Settling Defendant is

both a manufacturer and a retailer of the Calcium Product date

cf shipment shall mean the date on which a Calcium Product is

transferred from the manufacturing segment of the Settling

Defendants business

13 The Peoples Complaint alleges that Settling

Defendants through the sale of Calcium Products to consumers in

California violated provisions of the Safe Drinking Water and

Toxic Enforcement Act of 1986 Health and Safety Code

sections 252495 et seq (Proposition 65) and Business and

Professions Code sections 1 7200 et seq (Unfair Competition

Act) by knowingly exposing persons to lEiad a chemical known to

the State of California to cause reproductive toxicity without

first providing a clear and reasonable warning to such

25 individuals

14 For purposes of this Permanent Injunction only the

parties stipulate that this Court has jurisdiction over the

26

27

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 3

I

1

2

3

4

5

6

7

8

9

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11

16

18

19

2 0

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21 11

22

23 IiI

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middot1 25

26

allegations of violations contained in the Complaint and personal

jurisdiction over the Settling Defendants as to the acts alleged

in the Complaint that venue is proper in the City and County of

San Francisco and that this Court has jurisdiction to enter this

Permanent Injunction

15 The parties enter into this Permanent Injunction

pursuant to a settlement of certain disputed claims between the

parties as alleged in the Complaint for the purpose of avoiding

prolonged and costly litigation between the parties hereto By

execution of this Permanent Injunction Settling Defendants

individually and collectively do not admit any facts or

conclusions of law suggesting or demonstrating any violations of

Proposition 65 the Unfair Competition Act or any other

statutory common law or equitable requirements relating to

Calcium Products Nothing in this Permanent Injunction shall be

construed as an admission by Settling Defendants of any fact

issue of law or violation of law nor shall compliance with the

Permanent Injunction constitute or be construed as an admission

by such Settling Defendants of any fact issue of law or

violation of law Nothing in this Permarnmt Injunction shall

prejudice waive or impair any right remedy or defense such

Settling Defendants may have in this or any other or future legal

proceedings However this paragraph shall not diminish or otherwise affect the obligations responsibilities and duties of

such Settling Defendants individually or collectively under

ttis Permanent Injunction

2 Injunctive Relief - Warning Program

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 4 bull

1

2

3

4

S

6

7

8

9

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11

12

13

14

15

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17

18

19

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21

22

24

25

26

27

21 Where required herein clear and reasonable warning

that use of Calcium Products exposes persons to lead a chemical

known to the State of California to cause birth defects or other

reproductive harm shall be provided by a Settling Defendant in

the manner provided in this Permanent Injunction

22 A Settling Defendant shall provide a warning pursuant

to paragraph 2 5 for each Calcium Product whose date of shipment

is on or after July 1 1997 unless the Settling Defendant can

show pursuant to paragraph 210 and the testing protocol set

forth in Exhibit A attached to this Permanent Injunction that

the Calcium Product causes a total daily exposure to lead of 05

micrograms or less based on the amount of the Calcium Product

supplying a thousand (1000) milligrams of elemental calcium

II excluding any naturally occurring lead in the Calcium Product as

set forth in paragraph 23 below For those Calcium Products

where the recommended or maximum daily dose supplies more than

1500 milligrams of calcium a Settling Defendant shall provide a

I warning unless the Settling Defendant can show pursuant to

paragraph 210 and the testing protocol set forth in attached

i Exhibit A that the recommended daily dose of the Calcium Product

causes a total daily exposure to lead equal to or less than that

set forth in paragraph 24 below

23 A Settling Defendant shall be entitled to exclude from

the calculation of the daily lead exposure caused by a Calcium

Product the amount of lead per 1000 milligrams of calcium as set

forth in Table 23 of this paragraph 23 Compliance with this

Permanent Injunction is established and no warning is required

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 5

1

2

3

4

5

6

7

8

9

10

Jl

12

3

14

1 5

26

under Proposition 65 where the lead exposure caused by an amount

of the Calcium Product supplying 1000 milligrams of calcium does

d not exceed the sum of (a) 05 micrograms of lead per thousand

milligrams of elemental calcium and (b) the amount of lead

excluded on the date of shipment as naturally occurring

pursuant to Table 23 of this paragraph 23 For purposes of

this Permanent Injunction Table 23 of this paragraph 23 sets

forth the amount of lead per 1000 milligrams of elemental calcium

which shall be deemed to be naturally occurring at the lowest

level currently feasible pursuant to Section 12501 of Title 22

cf the California Code of Regulations (CCR) The amounts of

lead and dates set forth in Table 23 shall apply as of the date

of shipment of the Calcium Product

TABLE 2 3

DATE NATURALLY OCCURRING AMOUNT OF LEAD PER 1000 MILLIGRAMS OF CALCIUM

July 1 1997 35 micrograms

April 1 1999 10 microgram

24 Even if no warning is required by paragraphs 22 and

23 above in the event that the recommended daily dose of any

Calcium Product as specified on the label or in any other

package material exceeds 1500 milligrams a Settling Defendant

shall provide a warning pursuant to Propcsition 65 if the total

daily lead exposure from the Calcium Product based on the

recommended daily dose exceeds 150 of the level that would

require a warning pursuant to paragraphs 22 and 23 (based on a

an amount of the Calcium Product supplying 1000 milligrams of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 6

23

27

1

2

3

4

5 J

6

7

8

9

10

11

12

J 8

2 1 1

2 5

27

calcium) above as of the date of shipment of the Calcium Product

For antacids that do not have a recommended daily dose for

purposes of this Permanent Injunction the term recommended

daily dose shall mean two-thirds of the maximum daily dose as

set forth on the label or in any other package material

25 For a Calcium Product that does not meet the standards

set forth in paragraphs 2 2 through 2 4 above a Settling

Defendant shall at the point of manufacture prior to shipment

to California or prior to distribution within California (1)

affix to or print on the Calcium Product container cap label or

unit package or (2) display at the point of sale of the Calcium

Product the following warning (the language in brackets in the

warning below is optional)

WARNING This product contains [lead] a chemical known [to the State of California] to cause birth defects or other reproductive harm

26 The warning required by paragraph 25 above shall be

prominently affixed to printed on or displayed proximately to

the point-of-sale of each Calcium Product with such

conspicuousness as compared with other words statements

designs or devices on the labeling as to render it likely to be

read and understood by an ordinary individual under customary

conditions of purchase or use If the warning is displayed on

the product container or labeling the warning shall be at least

the same size as the largest of any other health or safety

warnings on the product container or labeling and the word

warning 11 shall be in all capital letters and in bold print If

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 7

1

2

3

4

5

6

7

B

9

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11

12

14

1 5

19

20

21

22

23

24

25

26

27

printed on the labeling itself the warning shall be contained in

the same section of the labeling that states other safety

warnings concerning the use of the product The Attorney General

agrees to review any labeling or point of sale signs proposed to

be used under this section and advise the Settling Defendant as

to whether he believes such labeling or point of sale signs

comply with this section The requirement for product labeling

set forth herein is imposed pursuant to the terms of this

Permanent Injunction and is recognized by the parties as not

being the exclusive method of providing a warning under

Proposition 65 and its implementing regulations for the Calcium

Products

27 In the event that the Attorney General determines that

the naturally occurring levels set forth in Table 23 of

paragraph 23 above are higher than the lowest level currently

feasible as stated in 22 CCR section 12501 (a) (4) he shall have

the right to seek a modification of the Permanent Injunction to

reflect the alleged lowest level currently feasible of

naturally occurring lead in the Calcium Products Prior to

seeking such modification the Attorney General shall provide

written notice to the Settling Defendants that he intends to seek

the modification The parties shall have ninety (90) days in

which to confer with the Attorney General concerning the

modification If one or more of the Settling Defendants and the

Attorney General are unable to agree on a modification to the

Permanent Injunction the Attorney General may file a motion with

the court seeking a modification of the Permanent Injunction

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

I AMOUNT 8

1

2

3

4

5

6

7

B

9

10

11 1

12

13

14

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16

17

18

19

2

2

2

23

24

25

26

2-1

In any motion by the Attorney General seeking such a

modification the burden of producing evidence shall be initially

upon the Attorney General to demonstrate a prima facie case that

the modification sought by the Attorney General is the lowest

level currently feasible The Settling Defendants who do not

agree to such modification retain the ultimate burden of proving

that the modification sought by the Attorney General is lower

than the lowest level currently feasible The parties hereby

agree that the Permanent Injunction should be modified to reflect

any agreement of the parties or any deterrrination by the Court

concerning what is the lowest level currently feasible for lead

in Calcium Products

28 In the event that Settling Defendants individually or

coilectively determine that the naturally occurring levels set

forth in Table 23 of paragraph 23 above are lower than the

lowest level currently feasible as stated in 22 CCR section

1250l(a) (4) such Settling Defendants shall have the right to

seek modification of the Permanent Injunction to reflect the

alleged lowest level currently feasible Prior to seeking such

modification such Settling Defendants shall provide written

notice to the Attorney General that they intend to seek the

modification The parties shall have ninety (90) days in which

to confer concerning the modification If the parties are unable

to agree on a modification to the Permanent Injunction such

Settling Defendants may file a motion with the Court seeking a

modification of the Permanent Injunction In any motion by

Settling Defendants seeking such modification the burden of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 9

1

1

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producing evidence and of proof shall be on such Settling

Defendants to prove that the modification sought by the Settling

Defendants is the lowest level currently feasible The parties

hereby agree that the Permanent Injunction should be modified to

reflect any agreement of the parties or any determination by the

Court concerning what is the lowest level currently feasible

I for lead in Calcium Products

29 The term feasible as used in paragraphs 27 and 28

above includes but is not limited to a consideration of the

following factors availability and reliabilityof a supply of

low-lead calcium that meets the requirememts set forth in

paragraphs 22 23 and 24 above cost of low-lead calcium and

resulting increase in manufacturers prices resulting from the

use of the low-lead calcium performance characteristics of lowshy

lead calcium and of the resulting Calcium Product including but

middot not limited to formulation performance safety efficacy and

stability Nothing in this Permanent Injunction shall be

interpreted to require the Settling Defendants to use any calcium

material as an ingredient in a Calcium Product that would render

i their Calcium Product unlawful under state or federal law as

measured by existing andor future applicable California and

federal food and drug laws and regulations Nothing in this

Permanent Injunction shall be interpreted to preclude a Settling

Defendant from advocating for purposes of paragraphs 27 andor

28 that any proposed modification requiring a change in the type

of raw calcium source material as an ingredient in a Calcium

Product is not feasible as defined herein Nothing in this

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 10

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Permanent Injunction shall be interpreted to preclude the People

from advocating for purposes of paragraphs 2 7 andor 2 8 that

any proposed modification requiring a change in the type of raw

Calcium source material as an ingredient in a calcium product is

feasible as defined herein

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210 Each Settling Defendant shall maintain records

sufficient to establish its compliance with this Permanent

Injunction for a period of four years following the date of

shipment of any Calcium Product into California Such documents

shall be sufficient in detail to establish compliance with the

Protocol set forth in the attached Exhibit A Upon reasonable written notice from the Attorney Generals Office a Settling

Defendant must produce to the Attorney General within ten (10)

tusiness days of the receipt of the Attorney Generals notice

the documents required to be maintained according to this

paragraph To the extent that such documents contain information

which the Settling Defendant maintains is confidential

proprietary andor in the nature of a trade secret (or in fact a

trade secret) and upon written notice as to the asserted

confidential nature of this information by the Settling

Defendant the Attorney General agrees not to disclose this

information to third parties (though the Attorney General may

disclose this information to its attorneys and employees

including professional consultants provided that these persons

also agree to maintain the confidentiality of the information in

these documents) In addition any Settling Defendant may

designate as confidential trade secret information as that term

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 11

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is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

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shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

21

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7

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

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2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

l

2

3

4

E

7

8 1

9 1

c I

~l

~t

_

2)

21

22 1

Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

8

l

1 )

1L

l L

l

- C

8

bull =

)()

) I

22

23

24

25

26

27

i I

ii

for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

I

IIi

2 1111

31

4 I

) II 11

1~ 11 ii

7 fl

s II 1

g 1 I

l )

for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

middotJC-~ J 14~ LJ - ---lt__

Its S-~ LIL~~ Pr-ltt-S1J~L

Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

2

~ li

4

5 middot

E

E

C

the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

8

_ _

---

-

6

Its

Dated CONSAC

By

Its

APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

3

Dated

7

8

Dated 7997

l ) AP PROVED AS TO FORM

Dated

l -~

~ IS SO ORDERED

By

Its

NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

L c

2 l

2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

C

6

7

8

g

0

11

12

15

16

1 7

8

19

21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

lbull9116I 21 11Jl

I

Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

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Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 5: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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Webster Street 12th Floor Oakland California 94612-3049)

5 Additional Enforcement Actions Continuing Obligations

5 1 By entering into this Consent Judgment the People do not waive any right to

take further enforcement actions on any violations not covered by the Complaint Nothing in

this Consent Judgment shall be construed as diminishing Bayers continuing obligation to

comply with Proposition 65 or the Unfair Competition Act in its future activities

6 Enforcement of Consent Judgment

6 1 The People may by motion or order to show cause before the Superior Court

of San Francisco enforce the terms and conditions contained in this Consent Judgment In

any action brought by the People to enforce this Consent Judgment the People may seek

whatever fines costs penalties or remedies as provided by law for failure to comply with the

Consent Judgment Where said failure to comply constitutes future violations of Proposition

65 or other laws independent of the Consent Judgment andor those alleged in the

Complaint the People are not limited to enforcement of this Consent Judgment but may

seek in another action whatever fines costs penalties or remedies are provided by law for

failure to comply with Proposition 65 or other laws The rights of Bayer to defend itself and

its actions in law or equity shall not be abrogated or reduced in any fashion by the terms of

this paragraph

7 Application of Consent Judgment

71 The Consent Judgment shall apply to be binding upon and inure to the benefit

of the parties their divisions subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 Authority to Stipulate to Consent Judgment

81 Each signatory to this Consent Judgment certifies that he or she is fully

authorized by the party he or she represents to enter into this Consent Judgment on behalf of

the party represented and legally to bind that party

I

STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND

I ORDER THEREON 5

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9 Claims Covered

91 This Consent Judgment is a final and binding resolution between the People

and Bayer of any and all alleged violations of Proposition 65 the Business and Professions

Code Sections 17200 et seq aandor the Consumers Legal Remedies Act Civil Code section

1750 et seq up through the date of entry of this Consent Judgment arising from failure to

warn of exposure to lead from consumption of Bayers Calcium Products or those of any

corporate affiliate that was committed by Bayer or by any entity within its respective chain

of distribution including but not limited to distributors wholesalers and retailers of any of

Bavers Calcium Products

10 Modification

10 1 This Consent Judgment may be modified from time to time by express written

agreement of Bayer and the Attorney General with the approval of the Court or by an order

of this Court

11 Execution in Counterparts

11 1 This Consent Judgment may be executed in counterparts which taken together

shall be deemed to constitute one and the same document

17 12 Entry of Stipulation for Entry of Consent Judgment Required

12 l This Stipulation for Entry of Consent Judgment shall be null and void and be

without any force or effect unless entered by the Court in this matter If the Stipulation for

Entry of Consent Judgment is not entered by the Court the execution of this Stipulation for

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STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 6

--------

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1 Entry of Consent Judgment by Bayer shall not be construed as an admission- by Bayer of any

fact issue of law or violation of law

IT IS SO STIPULATED

2

3

4 Dated 1-k98I I

1998 DANIEL E LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

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i3 BA YER CORPORATION

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Dep Attorneys General

By

DatedJ-eeuro-shy 4 l7itf

By

T)t~ 5vmiddot Ko1pon

Vice PresidentIts

APPROVED AS TO FORM

Dated -qf4 ORRICK HERRINGTON amp SUTCLIFFE

ll~-~By BRUCE KLAFTER Esq Attorneys for Bayer Corporation

IT IS SO ORDERED - 1- middot I L i - L

Dated

)

LUCY ltELLY McCABEPre~lding Judge

JUDGE SUPERIOR COURT CITY AND COUNTY OF SAN FRANCISCO

STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 7

EXHIBIT A

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) ) ) ) ) ) ) ) ) ) ) )

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 1

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON Supervising Deputy Attorney General

EDWARD G WEIL SUSAN S FIERING (State Bar No 121621)

Deputy Attorneys General 2101 Webster Street 12th Floor Oakland CA 94612-3049 Telephone (510) 286-3892

Attorneys for the People

SUPERIOR COURT OF THE STATE OF CALIFORNIA

FOR THE CITY AND COUNTY OF SAN FRANCISCO

PEOPLE OF THE STATE OF CALIFORNIA ex rel DANIELE LUNGREN Attorney)General of the State of California)

Plaintiffs V

WARNER-LAMBERT CO SMITHKLINE BEECHAM CORP AMERICAN HOME PRODUCTS CORP SOURCE NATURAL INC SCHERING-PLOUGH HEALTH CARE PRODUCTS INC PHARMAVITE CORP GENERAL NUTRITION CORP PERRIGO CO TWIN LABORATORIES INC and DOES 1-200

II Defendants i

No 984503

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND FOR PAYMENT OF SETTLEMENT AMOUNT AND ORDER THEREON

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Plaintiff the People of the State of California (People)

and defendants Bayer Corporation Johnson amp JohnsonMerck

Consumer Pharmaceuticals Nutrilite a Division of Amway

Corporation and Consac (hereinafter collectively Settling

Defendants) herein enter into this Stipulation for Entry of

Permanent Injunction and for Payment of Settlement Amount

(hereinafter Permanent Injunction) as follows

1 Introduction

11 On February 6 1997 the People of the State of

California ex rel Daniel E Lungren (People) filed a

Complaint for Civil Penalties and Injunctive Relief (Complaint)

in the Superior Court of the State of California City and County

of San Francisco against certain defendants On June 5 1997

the People served the Settling Defendants as Does No 5 through 8

respectively

12 Settling Defendants are companies that employ more

than ten persons and offer for sale within the State of

California one or more of the following calcium-containing

products (hereinafter Calcium Products) which are intended to

be ingested by human beings (a) products containing primarily

calcium that are intended to provide all or a major portion of

the recommended daily allowance of calcium (hereinafter Calcium

Supplements) (b) antacid products containing calcium

(hereinafter Antacids) and (c) dietary supplements as defined

in the federal Dietary Supplements Health and Education Act

Public Law no 103-417 108 Stat 4325 (1994) 21 USC sect

321(ff) containing calcium other than Calcium Supplements or

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION

II AND PAYMENT OF SETTLEMENT AMOUNT 2

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Antacids (hereinafter Multiple VitaminsMinerals)

Notwitthstanding any form of packaging of two or more different

alcium Products together the requirements of this Permanent

Injunction shall apply separately to each such different Calcium

froduct The term calcium as used in this Permanent Injunction

means elemental calcium when referring to an amount of calcium

and means any form or salt of calcium when referring to calcium

as an ingredient (active or inactive) in a Calcium Product For purposes of this Permanent Injunction the date of shipment

shall be the date on which the Calcium Product first enters the

stream of commerce except that where a Settling Defendant is

both a manufacturer and a retailer of the Calcium Product date

cf shipment shall mean the date on which a Calcium Product is

transferred from the manufacturing segment of the Settling

Defendants business

13 The Peoples Complaint alleges that Settling

Defendants through the sale of Calcium Products to consumers in

California violated provisions of the Safe Drinking Water and

Toxic Enforcement Act of 1986 Health and Safety Code

sections 252495 et seq (Proposition 65) and Business and

Professions Code sections 1 7200 et seq (Unfair Competition

Act) by knowingly exposing persons to lEiad a chemical known to

the State of California to cause reproductive toxicity without

first providing a clear and reasonable warning to such

25 individuals

14 For purposes of this Permanent Injunction only the

parties stipulate that this Court has jurisdiction over the

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 3

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allegations of violations contained in the Complaint and personal

jurisdiction over the Settling Defendants as to the acts alleged

in the Complaint that venue is proper in the City and County of

San Francisco and that this Court has jurisdiction to enter this

Permanent Injunction

15 The parties enter into this Permanent Injunction

pursuant to a settlement of certain disputed claims between the

parties as alleged in the Complaint for the purpose of avoiding

prolonged and costly litigation between the parties hereto By

execution of this Permanent Injunction Settling Defendants

individually and collectively do not admit any facts or

conclusions of law suggesting or demonstrating any violations of

Proposition 65 the Unfair Competition Act or any other

statutory common law or equitable requirements relating to

Calcium Products Nothing in this Permanent Injunction shall be

construed as an admission by Settling Defendants of any fact

issue of law or violation of law nor shall compliance with the

Permanent Injunction constitute or be construed as an admission

by such Settling Defendants of any fact issue of law or

violation of law Nothing in this Permarnmt Injunction shall

prejudice waive or impair any right remedy or defense such

Settling Defendants may have in this or any other or future legal

proceedings However this paragraph shall not diminish or otherwise affect the obligations responsibilities and duties of

such Settling Defendants individually or collectively under

ttis Permanent Injunction

2 Injunctive Relief - Warning Program

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 4 bull

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21 Where required herein clear and reasonable warning

that use of Calcium Products exposes persons to lead a chemical

known to the State of California to cause birth defects or other

reproductive harm shall be provided by a Settling Defendant in

the manner provided in this Permanent Injunction

22 A Settling Defendant shall provide a warning pursuant

to paragraph 2 5 for each Calcium Product whose date of shipment

is on or after July 1 1997 unless the Settling Defendant can

show pursuant to paragraph 210 and the testing protocol set

forth in Exhibit A attached to this Permanent Injunction that

the Calcium Product causes a total daily exposure to lead of 05

micrograms or less based on the amount of the Calcium Product

supplying a thousand (1000) milligrams of elemental calcium

II excluding any naturally occurring lead in the Calcium Product as

set forth in paragraph 23 below For those Calcium Products

where the recommended or maximum daily dose supplies more than

1500 milligrams of calcium a Settling Defendant shall provide a

I warning unless the Settling Defendant can show pursuant to

paragraph 210 and the testing protocol set forth in attached

i Exhibit A that the recommended daily dose of the Calcium Product

causes a total daily exposure to lead equal to or less than that

set forth in paragraph 24 below

23 A Settling Defendant shall be entitled to exclude from

the calculation of the daily lead exposure caused by a Calcium

Product the amount of lead per 1000 milligrams of calcium as set

forth in Table 23 of this paragraph 23 Compliance with this

Permanent Injunction is established and no warning is required

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 5

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under Proposition 65 where the lead exposure caused by an amount

of the Calcium Product supplying 1000 milligrams of calcium does

d not exceed the sum of (a) 05 micrograms of lead per thousand

milligrams of elemental calcium and (b) the amount of lead

excluded on the date of shipment as naturally occurring

pursuant to Table 23 of this paragraph 23 For purposes of

this Permanent Injunction Table 23 of this paragraph 23 sets

forth the amount of lead per 1000 milligrams of elemental calcium

which shall be deemed to be naturally occurring at the lowest

level currently feasible pursuant to Section 12501 of Title 22

cf the California Code of Regulations (CCR) The amounts of

lead and dates set forth in Table 23 shall apply as of the date

of shipment of the Calcium Product

TABLE 2 3

DATE NATURALLY OCCURRING AMOUNT OF LEAD PER 1000 MILLIGRAMS OF CALCIUM

July 1 1997 35 micrograms

April 1 1999 10 microgram

24 Even if no warning is required by paragraphs 22 and

23 above in the event that the recommended daily dose of any

Calcium Product as specified on the label or in any other

package material exceeds 1500 milligrams a Settling Defendant

shall provide a warning pursuant to Propcsition 65 if the total

daily lead exposure from the Calcium Product based on the

recommended daily dose exceeds 150 of the level that would

require a warning pursuant to paragraphs 22 and 23 (based on a

an amount of the Calcium Product supplying 1000 milligrams of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 6

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calcium) above as of the date of shipment of the Calcium Product

For antacids that do not have a recommended daily dose for

purposes of this Permanent Injunction the term recommended

daily dose shall mean two-thirds of the maximum daily dose as

set forth on the label or in any other package material

25 For a Calcium Product that does not meet the standards

set forth in paragraphs 2 2 through 2 4 above a Settling

Defendant shall at the point of manufacture prior to shipment

to California or prior to distribution within California (1)

affix to or print on the Calcium Product container cap label or

unit package or (2) display at the point of sale of the Calcium

Product the following warning (the language in brackets in the

warning below is optional)

WARNING This product contains [lead] a chemical known [to the State of California] to cause birth defects or other reproductive harm

26 The warning required by paragraph 25 above shall be

prominently affixed to printed on or displayed proximately to

the point-of-sale of each Calcium Product with such

conspicuousness as compared with other words statements

designs or devices on the labeling as to render it likely to be

read and understood by an ordinary individual under customary

conditions of purchase or use If the warning is displayed on

the product container or labeling the warning shall be at least

the same size as the largest of any other health or safety

warnings on the product container or labeling and the word

warning 11 shall be in all capital letters and in bold print If

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 7

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printed on the labeling itself the warning shall be contained in

the same section of the labeling that states other safety

warnings concerning the use of the product The Attorney General

agrees to review any labeling or point of sale signs proposed to

be used under this section and advise the Settling Defendant as

to whether he believes such labeling or point of sale signs

comply with this section The requirement for product labeling

set forth herein is imposed pursuant to the terms of this

Permanent Injunction and is recognized by the parties as not

being the exclusive method of providing a warning under

Proposition 65 and its implementing regulations for the Calcium

Products

27 In the event that the Attorney General determines that

the naturally occurring levels set forth in Table 23 of

paragraph 23 above are higher than the lowest level currently

feasible as stated in 22 CCR section 12501 (a) (4) he shall have

the right to seek a modification of the Permanent Injunction to

reflect the alleged lowest level currently feasible of

naturally occurring lead in the Calcium Products Prior to

seeking such modification the Attorney General shall provide

written notice to the Settling Defendants that he intends to seek

the modification The parties shall have ninety (90) days in

which to confer with the Attorney General concerning the

modification If one or more of the Settling Defendants and the

Attorney General are unable to agree on a modification to the

Permanent Injunction the Attorney General may file a motion with

the court seeking a modification of the Permanent Injunction

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

I AMOUNT 8

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In any motion by the Attorney General seeking such a

modification the burden of producing evidence shall be initially

upon the Attorney General to demonstrate a prima facie case that

the modification sought by the Attorney General is the lowest

level currently feasible The Settling Defendants who do not

agree to such modification retain the ultimate burden of proving

that the modification sought by the Attorney General is lower

than the lowest level currently feasible The parties hereby

agree that the Permanent Injunction should be modified to reflect

any agreement of the parties or any deterrrination by the Court

concerning what is the lowest level currently feasible for lead

in Calcium Products

28 In the event that Settling Defendants individually or

coilectively determine that the naturally occurring levels set

forth in Table 23 of paragraph 23 above are lower than the

lowest level currently feasible as stated in 22 CCR section

1250l(a) (4) such Settling Defendants shall have the right to

seek modification of the Permanent Injunction to reflect the

alleged lowest level currently feasible Prior to seeking such

modification such Settling Defendants shall provide written

notice to the Attorney General that they intend to seek the

modification The parties shall have ninety (90) days in which

to confer concerning the modification If the parties are unable

to agree on a modification to the Permanent Injunction such

Settling Defendants may file a motion with the Court seeking a

modification of the Permanent Injunction In any motion by

Settling Defendants seeking such modification the burden of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 9

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producing evidence and of proof shall be on such Settling

Defendants to prove that the modification sought by the Settling

Defendants is the lowest level currently feasible The parties

hereby agree that the Permanent Injunction should be modified to

reflect any agreement of the parties or any determination by the

Court concerning what is the lowest level currently feasible

I for lead in Calcium Products

29 The term feasible as used in paragraphs 27 and 28

above includes but is not limited to a consideration of the

following factors availability and reliabilityof a supply of

low-lead calcium that meets the requirememts set forth in

paragraphs 22 23 and 24 above cost of low-lead calcium and

resulting increase in manufacturers prices resulting from the

use of the low-lead calcium performance characteristics of lowshy

lead calcium and of the resulting Calcium Product including but

middot not limited to formulation performance safety efficacy and

stability Nothing in this Permanent Injunction shall be

interpreted to require the Settling Defendants to use any calcium

material as an ingredient in a Calcium Product that would render

i their Calcium Product unlawful under state or federal law as

measured by existing andor future applicable California and

federal food and drug laws and regulations Nothing in this

Permanent Injunction shall be interpreted to preclude a Settling

Defendant from advocating for purposes of paragraphs 27 andor

28 that any proposed modification requiring a change in the type

of raw calcium source material as an ingredient in a Calcium

Product is not feasible as defined herein Nothing in this

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 10

ii

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Permanent Injunction shall be interpreted to preclude the People

from advocating for purposes of paragraphs 2 7 andor 2 8 that

any proposed modification requiring a change in the type of raw

Calcium source material as an ingredient in a calcium product is

feasible as defined herein

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210 Each Settling Defendant shall maintain records

sufficient to establish its compliance with this Permanent

Injunction for a period of four years following the date of

shipment of any Calcium Product into California Such documents

shall be sufficient in detail to establish compliance with the

Protocol set forth in the attached Exhibit A Upon reasonable written notice from the Attorney Generals Office a Settling

Defendant must produce to the Attorney General within ten (10)

tusiness days of the receipt of the Attorney Generals notice

the documents required to be maintained according to this

paragraph To the extent that such documents contain information

which the Settling Defendant maintains is confidential

proprietary andor in the nature of a trade secret (or in fact a

trade secret) and upon written notice as to the asserted

confidential nature of this information by the Settling

Defendant the Attorney General agrees not to disclose this

information to third parties (though the Attorney General may

disclose this information to its attorneys and employees

including professional consultants provided that these persons

also agree to maintain the confidentiality of the information in

these documents) In addition any Settling Defendant may

designate as confidential trade secret information as that term

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 11

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is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

11

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12

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17

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shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

21

l

2

3

4

5

6

7

8

9

1G

11

2

3

14

JI

~7

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~9

20

i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

22

23

24 [l

25 II I

26

2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

II al - Ii

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

l

2

3

4

E

7

8 1

9 1

c I

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21

22 1

Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

8

l

1 )

1L

l L

l

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8

bull =

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22

23

24

25

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for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

I

IIi

2 1111

31

4 I

) II 11

1~ 11 ii

7 fl

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for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

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Its S-~ LIL~~ Pr-ltt-S1J~L

Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

2

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4

5 middot

E

E

C

the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

8

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---

-

6

Its

Dated CONSAC

By

Its

APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

3

Dated

7

8

Dated 7997

l ) AP PROVED AS TO FORM

Dated

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~ IS SO ORDERED

By

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NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

L c

2 l

2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

C

6

7

8

g

0

11

12

15

16

1 7

8

19

21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

lbull9116I 21 11Jl

I

Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

l-litl~ 4ll lUl

Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

l HI l 6l Vl l I IJ2

Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 6: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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9 Claims Covered

91 This Consent Judgment is a final and binding resolution between the People

and Bayer of any and all alleged violations of Proposition 65 the Business and Professions

Code Sections 17200 et seq aandor the Consumers Legal Remedies Act Civil Code section

1750 et seq up through the date of entry of this Consent Judgment arising from failure to

warn of exposure to lead from consumption of Bayers Calcium Products or those of any

corporate affiliate that was committed by Bayer or by any entity within its respective chain

of distribution including but not limited to distributors wholesalers and retailers of any of

Bavers Calcium Products

10 Modification

10 1 This Consent Judgment may be modified from time to time by express written

agreement of Bayer and the Attorney General with the approval of the Court or by an order

of this Court

11 Execution in Counterparts

11 1 This Consent Judgment may be executed in counterparts which taken together

shall be deemed to constitute one and the same document

17 12 Entry of Stipulation for Entry of Consent Judgment Required

12 l This Stipulation for Entry of Consent Judgment shall be null and void and be

without any force or effect unless entered by the Court in this matter If the Stipulation for

Entry of Consent Judgment is not entered by the Court the execution of this Stipulation for

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STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 6

--------

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1 Entry of Consent Judgment by Bayer shall not be construed as an admission- by Bayer of any

fact issue of law or violation of law

IT IS SO STIPULATED

2

3

4 Dated 1-k98I I

1998 DANIEL E LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

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i3 BA YER CORPORATION

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2-middot

Dep Attorneys General

By

DatedJ-eeuro-shy 4 l7itf

By

T)t~ 5vmiddot Ko1pon

Vice PresidentIts

APPROVED AS TO FORM

Dated -qf4 ORRICK HERRINGTON amp SUTCLIFFE

ll~-~By BRUCE KLAFTER Esq Attorneys for Bayer Corporation

IT IS SO ORDERED - 1- middot I L i - L

Dated

)

LUCY ltELLY McCABEPre~lding Judge

JUDGE SUPERIOR COURT CITY AND COUNTY OF SAN FRANCISCO

STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 7

EXHIBIT A

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 1

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON Supervising Deputy Attorney General

EDWARD G WEIL SUSAN S FIERING (State Bar No 121621)

Deputy Attorneys General 2101 Webster Street 12th Floor Oakland CA 94612-3049 Telephone (510) 286-3892

Attorneys for the People

SUPERIOR COURT OF THE STATE OF CALIFORNIA

FOR THE CITY AND COUNTY OF SAN FRANCISCO

PEOPLE OF THE STATE OF CALIFORNIA ex rel DANIELE LUNGREN Attorney)General of the State of California)

Plaintiffs V

WARNER-LAMBERT CO SMITHKLINE BEECHAM CORP AMERICAN HOME PRODUCTS CORP SOURCE NATURAL INC SCHERING-PLOUGH HEALTH CARE PRODUCTS INC PHARMAVITE CORP GENERAL NUTRITION CORP PERRIGO CO TWIN LABORATORIES INC and DOES 1-200

II Defendants i

No 984503

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND FOR PAYMENT OF SETTLEMENT AMOUNT AND ORDER THEREON

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Plaintiff the People of the State of California (People)

and defendants Bayer Corporation Johnson amp JohnsonMerck

Consumer Pharmaceuticals Nutrilite a Division of Amway

Corporation and Consac (hereinafter collectively Settling

Defendants) herein enter into this Stipulation for Entry of

Permanent Injunction and for Payment of Settlement Amount

(hereinafter Permanent Injunction) as follows

1 Introduction

11 On February 6 1997 the People of the State of

California ex rel Daniel E Lungren (People) filed a

Complaint for Civil Penalties and Injunctive Relief (Complaint)

in the Superior Court of the State of California City and County

of San Francisco against certain defendants On June 5 1997

the People served the Settling Defendants as Does No 5 through 8

respectively

12 Settling Defendants are companies that employ more

than ten persons and offer for sale within the State of

California one or more of the following calcium-containing

products (hereinafter Calcium Products) which are intended to

be ingested by human beings (a) products containing primarily

calcium that are intended to provide all or a major portion of

the recommended daily allowance of calcium (hereinafter Calcium

Supplements) (b) antacid products containing calcium

(hereinafter Antacids) and (c) dietary supplements as defined

in the federal Dietary Supplements Health and Education Act

Public Law no 103-417 108 Stat 4325 (1994) 21 USC sect

321(ff) containing calcium other than Calcium Supplements or

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION

II AND PAYMENT OF SETTLEMENT AMOUNT 2

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Antacids (hereinafter Multiple VitaminsMinerals)

Notwitthstanding any form of packaging of two or more different

alcium Products together the requirements of this Permanent

Injunction shall apply separately to each such different Calcium

froduct The term calcium as used in this Permanent Injunction

means elemental calcium when referring to an amount of calcium

and means any form or salt of calcium when referring to calcium

as an ingredient (active or inactive) in a Calcium Product For purposes of this Permanent Injunction the date of shipment

shall be the date on which the Calcium Product first enters the

stream of commerce except that where a Settling Defendant is

both a manufacturer and a retailer of the Calcium Product date

cf shipment shall mean the date on which a Calcium Product is

transferred from the manufacturing segment of the Settling

Defendants business

13 The Peoples Complaint alleges that Settling

Defendants through the sale of Calcium Products to consumers in

California violated provisions of the Safe Drinking Water and

Toxic Enforcement Act of 1986 Health and Safety Code

sections 252495 et seq (Proposition 65) and Business and

Professions Code sections 1 7200 et seq (Unfair Competition

Act) by knowingly exposing persons to lEiad a chemical known to

the State of California to cause reproductive toxicity without

first providing a clear and reasonable warning to such

25 individuals

14 For purposes of this Permanent Injunction only the

parties stipulate that this Court has jurisdiction over the

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 3

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allegations of violations contained in the Complaint and personal

jurisdiction over the Settling Defendants as to the acts alleged

in the Complaint that venue is proper in the City and County of

San Francisco and that this Court has jurisdiction to enter this

Permanent Injunction

15 The parties enter into this Permanent Injunction

pursuant to a settlement of certain disputed claims between the

parties as alleged in the Complaint for the purpose of avoiding

prolonged and costly litigation between the parties hereto By

execution of this Permanent Injunction Settling Defendants

individually and collectively do not admit any facts or

conclusions of law suggesting or demonstrating any violations of

Proposition 65 the Unfair Competition Act or any other

statutory common law or equitable requirements relating to

Calcium Products Nothing in this Permanent Injunction shall be

construed as an admission by Settling Defendants of any fact

issue of law or violation of law nor shall compliance with the

Permanent Injunction constitute or be construed as an admission

by such Settling Defendants of any fact issue of law or

violation of law Nothing in this Permarnmt Injunction shall

prejudice waive or impair any right remedy or defense such

Settling Defendants may have in this or any other or future legal

proceedings However this paragraph shall not diminish or otherwise affect the obligations responsibilities and duties of

such Settling Defendants individually or collectively under

ttis Permanent Injunction

2 Injunctive Relief - Warning Program

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 4 bull

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21 Where required herein clear and reasonable warning

that use of Calcium Products exposes persons to lead a chemical

known to the State of California to cause birth defects or other

reproductive harm shall be provided by a Settling Defendant in

the manner provided in this Permanent Injunction

22 A Settling Defendant shall provide a warning pursuant

to paragraph 2 5 for each Calcium Product whose date of shipment

is on or after July 1 1997 unless the Settling Defendant can

show pursuant to paragraph 210 and the testing protocol set

forth in Exhibit A attached to this Permanent Injunction that

the Calcium Product causes a total daily exposure to lead of 05

micrograms or less based on the amount of the Calcium Product

supplying a thousand (1000) milligrams of elemental calcium

II excluding any naturally occurring lead in the Calcium Product as

set forth in paragraph 23 below For those Calcium Products

where the recommended or maximum daily dose supplies more than

1500 milligrams of calcium a Settling Defendant shall provide a

I warning unless the Settling Defendant can show pursuant to

paragraph 210 and the testing protocol set forth in attached

i Exhibit A that the recommended daily dose of the Calcium Product

causes a total daily exposure to lead equal to or less than that

set forth in paragraph 24 below

23 A Settling Defendant shall be entitled to exclude from

the calculation of the daily lead exposure caused by a Calcium

Product the amount of lead per 1000 milligrams of calcium as set

forth in Table 23 of this paragraph 23 Compliance with this

Permanent Injunction is established and no warning is required

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 5

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under Proposition 65 where the lead exposure caused by an amount

of the Calcium Product supplying 1000 milligrams of calcium does

d not exceed the sum of (a) 05 micrograms of lead per thousand

milligrams of elemental calcium and (b) the amount of lead

excluded on the date of shipment as naturally occurring

pursuant to Table 23 of this paragraph 23 For purposes of

this Permanent Injunction Table 23 of this paragraph 23 sets

forth the amount of lead per 1000 milligrams of elemental calcium

which shall be deemed to be naturally occurring at the lowest

level currently feasible pursuant to Section 12501 of Title 22

cf the California Code of Regulations (CCR) The amounts of

lead and dates set forth in Table 23 shall apply as of the date

of shipment of the Calcium Product

TABLE 2 3

DATE NATURALLY OCCURRING AMOUNT OF LEAD PER 1000 MILLIGRAMS OF CALCIUM

July 1 1997 35 micrograms

April 1 1999 10 microgram

24 Even if no warning is required by paragraphs 22 and

23 above in the event that the recommended daily dose of any

Calcium Product as specified on the label or in any other

package material exceeds 1500 milligrams a Settling Defendant

shall provide a warning pursuant to Propcsition 65 if the total

daily lead exposure from the Calcium Product based on the

recommended daily dose exceeds 150 of the level that would

require a warning pursuant to paragraphs 22 and 23 (based on a

an amount of the Calcium Product supplying 1000 milligrams of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 6

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calcium) above as of the date of shipment of the Calcium Product

For antacids that do not have a recommended daily dose for

purposes of this Permanent Injunction the term recommended

daily dose shall mean two-thirds of the maximum daily dose as

set forth on the label or in any other package material

25 For a Calcium Product that does not meet the standards

set forth in paragraphs 2 2 through 2 4 above a Settling

Defendant shall at the point of manufacture prior to shipment

to California or prior to distribution within California (1)

affix to or print on the Calcium Product container cap label or

unit package or (2) display at the point of sale of the Calcium

Product the following warning (the language in brackets in the

warning below is optional)

WARNING This product contains [lead] a chemical known [to the State of California] to cause birth defects or other reproductive harm

26 The warning required by paragraph 25 above shall be

prominently affixed to printed on or displayed proximately to

the point-of-sale of each Calcium Product with such

conspicuousness as compared with other words statements

designs or devices on the labeling as to render it likely to be

read and understood by an ordinary individual under customary

conditions of purchase or use If the warning is displayed on

the product container or labeling the warning shall be at least

the same size as the largest of any other health or safety

warnings on the product container or labeling and the word

warning 11 shall be in all capital letters and in bold print If

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 7

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printed on the labeling itself the warning shall be contained in

the same section of the labeling that states other safety

warnings concerning the use of the product The Attorney General

agrees to review any labeling or point of sale signs proposed to

be used under this section and advise the Settling Defendant as

to whether he believes such labeling or point of sale signs

comply with this section The requirement for product labeling

set forth herein is imposed pursuant to the terms of this

Permanent Injunction and is recognized by the parties as not

being the exclusive method of providing a warning under

Proposition 65 and its implementing regulations for the Calcium

Products

27 In the event that the Attorney General determines that

the naturally occurring levels set forth in Table 23 of

paragraph 23 above are higher than the lowest level currently

feasible as stated in 22 CCR section 12501 (a) (4) he shall have

the right to seek a modification of the Permanent Injunction to

reflect the alleged lowest level currently feasible of

naturally occurring lead in the Calcium Products Prior to

seeking such modification the Attorney General shall provide

written notice to the Settling Defendants that he intends to seek

the modification The parties shall have ninety (90) days in

which to confer with the Attorney General concerning the

modification If one or more of the Settling Defendants and the

Attorney General are unable to agree on a modification to the

Permanent Injunction the Attorney General may file a motion with

the court seeking a modification of the Permanent Injunction

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

I AMOUNT 8

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In any motion by the Attorney General seeking such a

modification the burden of producing evidence shall be initially

upon the Attorney General to demonstrate a prima facie case that

the modification sought by the Attorney General is the lowest

level currently feasible The Settling Defendants who do not

agree to such modification retain the ultimate burden of proving

that the modification sought by the Attorney General is lower

than the lowest level currently feasible The parties hereby

agree that the Permanent Injunction should be modified to reflect

any agreement of the parties or any deterrrination by the Court

concerning what is the lowest level currently feasible for lead

in Calcium Products

28 In the event that Settling Defendants individually or

coilectively determine that the naturally occurring levels set

forth in Table 23 of paragraph 23 above are lower than the

lowest level currently feasible as stated in 22 CCR section

1250l(a) (4) such Settling Defendants shall have the right to

seek modification of the Permanent Injunction to reflect the

alleged lowest level currently feasible Prior to seeking such

modification such Settling Defendants shall provide written

notice to the Attorney General that they intend to seek the

modification The parties shall have ninety (90) days in which

to confer concerning the modification If the parties are unable

to agree on a modification to the Permanent Injunction such

Settling Defendants may file a motion with the Court seeking a

modification of the Permanent Injunction In any motion by

Settling Defendants seeking such modification the burden of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 9

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producing evidence and of proof shall be on such Settling

Defendants to prove that the modification sought by the Settling

Defendants is the lowest level currently feasible The parties

hereby agree that the Permanent Injunction should be modified to

reflect any agreement of the parties or any determination by the

Court concerning what is the lowest level currently feasible

I for lead in Calcium Products

29 The term feasible as used in paragraphs 27 and 28

above includes but is not limited to a consideration of the

following factors availability and reliabilityof a supply of

low-lead calcium that meets the requirememts set forth in

paragraphs 22 23 and 24 above cost of low-lead calcium and

resulting increase in manufacturers prices resulting from the

use of the low-lead calcium performance characteristics of lowshy

lead calcium and of the resulting Calcium Product including but

middot not limited to formulation performance safety efficacy and

stability Nothing in this Permanent Injunction shall be

interpreted to require the Settling Defendants to use any calcium

material as an ingredient in a Calcium Product that would render

i their Calcium Product unlawful under state or federal law as

measured by existing andor future applicable California and

federal food and drug laws and regulations Nothing in this

Permanent Injunction shall be interpreted to preclude a Settling

Defendant from advocating for purposes of paragraphs 27 andor

28 that any proposed modification requiring a change in the type

of raw calcium source material as an ingredient in a Calcium

Product is not feasible as defined herein Nothing in this

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 10

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Permanent Injunction shall be interpreted to preclude the People

from advocating for purposes of paragraphs 2 7 andor 2 8 that

any proposed modification requiring a change in the type of raw

Calcium source material as an ingredient in a calcium product is

feasible as defined herein

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210 Each Settling Defendant shall maintain records

sufficient to establish its compliance with this Permanent

Injunction for a period of four years following the date of

shipment of any Calcium Product into California Such documents

shall be sufficient in detail to establish compliance with the

Protocol set forth in the attached Exhibit A Upon reasonable written notice from the Attorney Generals Office a Settling

Defendant must produce to the Attorney General within ten (10)

tusiness days of the receipt of the Attorney Generals notice

the documents required to be maintained according to this

paragraph To the extent that such documents contain information

which the Settling Defendant maintains is confidential

proprietary andor in the nature of a trade secret (or in fact a

trade secret) and upon written notice as to the asserted

confidential nature of this information by the Settling

Defendant the Attorney General agrees not to disclose this

information to third parties (though the Attorney General may

disclose this information to its attorneys and employees

including professional consultants provided that these persons

also agree to maintain the confidentiality of the information in

these documents) In addition any Settling Defendant may

designate as confidential trade secret information as that term

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 11

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is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

11

l

2

3

4

~

6

7

8

9

1

11

12

J3

l 4

17

l 3

~l

~6

shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

21

l

2

3

4

5

6

7

8

9

1G

11

2

3

14

JI

~7

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~9

20

i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

22

23

24 [l

25 II I

26

2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

II al - Ii

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

l

2

3

4

E

7

8 1

9 1

c I

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21

22 1

Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

8

l

1 )

1L

l L

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8

bull =

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22

23

24

25

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27

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for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

I

IIi

2 1111

31

4 I

) II 11

1~ 11 ii

7 fl

s II 1

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for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

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Its S-~ LIL~~ Pr-ltt-S1J~L

Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

2

~ li

4

5 middot

E

E

C

the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

8

_ _

---

-

6

Its

Dated CONSAC

By

Its

APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

3

Dated

7

8

Dated 7997

l ) AP PROVED AS TO FORM

Dated

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By

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NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

L c

2 l

2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

C

6

7

8

g

0

11

12

15

16

1 7

8

19

21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

lbull9116I 21 11Jl

I

Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

l-litl~ 4ll lUl

Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

l HI l 6l Vl l I IJ2

Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 7: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

--------

--------------

1 Entry of Consent Judgment by Bayer shall not be construed as an admission- by Bayer of any

fact issue of law or violation of law

IT IS SO STIPULATED

2

3

4 Dated 1-k98I I

1998 DANIEL E LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

5

6

7

8

9

10

11

12

i3 BA YER CORPORATION

14

15

16

7 I

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19

2C

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2

2-middot

Dep Attorneys General

By

DatedJ-eeuro-shy 4 l7itf

By

T)t~ 5vmiddot Ko1pon

Vice PresidentIts

APPROVED AS TO FORM

Dated -qf4 ORRICK HERRINGTON amp SUTCLIFFE

ll~-~By BRUCE KLAFTER Esq Attorneys for Bayer Corporation

IT IS SO ORDERED - 1- middot I L i - L

Dated

)

LUCY ltELLY McCABEPre~lding Judge

JUDGE SUPERIOR COURT CITY AND COUNTY OF SAN FRANCISCO

STIPULATION FOR ENTRY OF CONSENT JUDGMENT AND ORDER THEREON 7

EXHIBIT A

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 1

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON Supervising Deputy Attorney General

EDWARD G WEIL SUSAN S FIERING (State Bar No 121621)

Deputy Attorneys General 2101 Webster Street 12th Floor Oakland CA 94612-3049 Telephone (510) 286-3892

Attorneys for the People

SUPERIOR COURT OF THE STATE OF CALIFORNIA

FOR THE CITY AND COUNTY OF SAN FRANCISCO

PEOPLE OF THE STATE OF CALIFORNIA ex rel DANIELE LUNGREN Attorney)General of the State of California)

Plaintiffs V

WARNER-LAMBERT CO SMITHKLINE BEECHAM CORP AMERICAN HOME PRODUCTS CORP SOURCE NATURAL INC SCHERING-PLOUGH HEALTH CARE PRODUCTS INC PHARMAVITE CORP GENERAL NUTRITION CORP PERRIGO CO TWIN LABORATORIES INC and DOES 1-200

II Defendants i

No 984503

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND FOR PAYMENT OF SETTLEMENT AMOUNT AND ORDER THEREON

5

10

15

20

25

1

2

3

4

6

7

8

9

11

12

13

14

16

17

18

19

21

22

23

24

26

27

Plaintiff the People of the State of California (People)

and defendants Bayer Corporation Johnson amp JohnsonMerck

Consumer Pharmaceuticals Nutrilite a Division of Amway

Corporation and Consac (hereinafter collectively Settling

Defendants) herein enter into this Stipulation for Entry of

Permanent Injunction and for Payment of Settlement Amount

(hereinafter Permanent Injunction) as follows

1 Introduction

11 On February 6 1997 the People of the State of

California ex rel Daniel E Lungren (People) filed a

Complaint for Civil Penalties and Injunctive Relief (Complaint)

in the Superior Court of the State of California City and County

of San Francisco against certain defendants On June 5 1997

the People served the Settling Defendants as Does No 5 through 8

respectively

12 Settling Defendants are companies that employ more

than ten persons and offer for sale within the State of

California one or more of the following calcium-containing

products (hereinafter Calcium Products) which are intended to

be ingested by human beings (a) products containing primarily

calcium that are intended to provide all or a major portion of

the recommended daily allowance of calcium (hereinafter Calcium

Supplements) (b) antacid products containing calcium

(hereinafter Antacids) and (c) dietary supplements as defined

in the federal Dietary Supplements Health and Education Act

Public Law no 103-417 108 Stat 4325 (1994) 21 USC sect

321(ff) containing calcium other than Calcium Supplements or

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION

II AND PAYMENT OF SETTLEMENT AMOUNT 2

1

2

3

4

5

6 I

7

8 I

9

middot

14

15

17

18

19

20

21

22

23

24

Antacids (hereinafter Multiple VitaminsMinerals)

Notwitthstanding any form of packaging of two or more different

alcium Products together the requirements of this Permanent

Injunction shall apply separately to each such different Calcium

froduct The term calcium as used in this Permanent Injunction

means elemental calcium when referring to an amount of calcium

and means any form or salt of calcium when referring to calcium

as an ingredient (active or inactive) in a Calcium Product For purposes of this Permanent Injunction the date of shipment

shall be the date on which the Calcium Product first enters the

stream of commerce except that where a Settling Defendant is

both a manufacturer and a retailer of the Calcium Product date

cf shipment shall mean the date on which a Calcium Product is

transferred from the manufacturing segment of the Settling

Defendants business

13 The Peoples Complaint alleges that Settling

Defendants through the sale of Calcium Products to consumers in

California violated provisions of the Safe Drinking Water and

Toxic Enforcement Act of 1986 Health and Safety Code

sections 252495 et seq (Proposition 65) and Business and

Professions Code sections 1 7200 et seq (Unfair Competition

Act) by knowingly exposing persons to lEiad a chemical known to

the State of California to cause reproductive toxicity without

first providing a clear and reasonable warning to such

25 individuals

14 For purposes of this Permanent Injunction only the

parties stipulate that this Court has jurisdiction over the

26

27

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 3

I

1

2

3

4

5

6

7

8

9

JC

11

16

18

19

2 0

I

21 11

22

23 IiI

24

middot1 25

26

allegations of violations contained in the Complaint and personal

jurisdiction over the Settling Defendants as to the acts alleged

in the Complaint that venue is proper in the City and County of

San Francisco and that this Court has jurisdiction to enter this

Permanent Injunction

15 The parties enter into this Permanent Injunction

pursuant to a settlement of certain disputed claims between the

parties as alleged in the Complaint for the purpose of avoiding

prolonged and costly litigation between the parties hereto By

execution of this Permanent Injunction Settling Defendants

individually and collectively do not admit any facts or

conclusions of law suggesting or demonstrating any violations of

Proposition 65 the Unfair Competition Act or any other

statutory common law or equitable requirements relating to

Calcium Products Nothing in this Permanent Injunction shall be

construed as an admission by Settling Defendants of any fact

issue of law or violation of law nor shall compliance with the

Permanent Injunction constitute or be construed as an admission

by such Settling Defendants of any fact issue of law or

violation of law Nothing in this Permarnmt Injunction shall

prejudice waive or impair any right remedy or defense such

Settling Defendants may have in this or any other or future legal

proceedings However this paragraph shall not diminish or otherwise affect the obligations responsibilities and duties of

such Settling Defendants individually or collectively under

ttis Permanent Injunction

2 Injunctive Relief - Warning Program

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 4 bull

1

2

3

4

S

6

7

8

9

lJ

11

12

13

14

15

16

17

18

19

2 O

21

22

24

25

26

27

21 Where required herein clear and reasonable warning

that use of Calcium Products exposes persons to lead a chemical

known to the State of California to cause birth defects or other

reproductive harm shall be provided by a Settling Defendant in

the manner provided in this Permanent Injunction

22 A Settling Defendant shall provide a warning pursuant

to paragraph 2 5 for each Calcium Product whose date of shipment

is on or after July 1 1997 unless the Settling Defendant can

show pursuant to paragraph 210 and the testing protocol set

forth in Exhibit A attached to this Permanent Injunction that

the Calcium Product causes a total daily exposure to lead of 05

micrograms or less based on the amount of the Calcium Product

supplying a thousand (1000) milligrams of elemental calcium

II excluding any naturally occurring lead in the Calcium Product as

set forth in paragraph 23 below For those Calcium Products

where the recommended or maximum daily dose supplies more than

1500 milligrams of calcium a Settling Defendant shall provide a

I warning unless the Settling Defendant can show pursuant to

paragraph 210 and the testing protocol set forth in attached

i Exhibit A that the recommended daily dose of the Calcium Product

causes a total daily exposure to lead equal to or less than that

set forth in paragraph 24 below

23 A Settling Defendant shall be entitled to exclude from

the calculation of the daily lead exposure caused by a Calcium

Product the amount of lead per 1000 milligrams of calcium as set

forth in Table 23 of this paragraph 23 Compliance with this

Permanent Injunction is established and no warning is required

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 5

1

2

3

4

5

6

7

8

9

10

Jl

12

3

14

1 5

26

under Proposition 65 where the lead exposure caused by an amount

of the Calcium Product supplying 1000 milligrams of calcium does

d not exceed the sum of (a) 05 micrograms of lead per thousand

milligrams of elemental calcium and (b) the amount of lead

excluded on the date of shipment as naturally occurring

pursuant to Table 23 of this paragraph 23 For purposes of

this Permanent Injunction Table 23 of this paragraph 23 sets

forth the amount of lead per 1000 milligrams of elemental calcium

which shall be deemed to be naturally occurring at the lowest

level currently feasible pursuant to Section 12501 of Title 22

cf the California Code of Regulations (CCR) The amounts of

lead and dates set forth in Table 23 shall apply as of the date

of shipment of the Calcium Product

TABLE 2 3

DATE NATURALLY OCCURRING AMOUNT OF LEAD PER 1000 MILLIGRAMS OF CALCIUM

July 1 1997 35 micrograms

April 1 1999 10 microgram

24 Even if no warning is required by paragraphs 22 and

23 above in the event that the recommended daily dose of any

Calcium Product as specified on the label or in any other

package material exceeds 1500 milligrams a Settling Defendant

shall provide a warning pursuant to Propcsition 65 if the total

daily lead exposure from the Calcium Product based on the

recommended daily dose exceeds 150 of the level that would

require a warning pursuant to paragraphs 22 and 23 (based on a

an amount of the Calcium Product supplying 1000 milligrams of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 6

23

27

1

2

3

4

5 J

6

7

8

9

10

11

12

J 8

2 1 1

2 5

27

calcium) above as of the date of shipment of the Calcium Product

For antacids that do not have a recommended daily dose for

purposes of this Permanent Injunction the term recommended

daily dose shall mean two-thirds of the maximum daily dose as

set forth on the label or in any other package material

25 For a Calcium Product that does not meet the standards

set forth in paragraphs 2 2 through 2 4 above a Settling

Defendant shall at the point of manufacture prior to shipment

to California or prior to distribution within California (1)

affix to or print on the Calcium Product container cap label or

unit package or (2) display at the point of sale of the Calcium

Product the following warning (the language in brackets in the

warning below is optional)

WARNING This product contains [lead] a chemical known [to the State of California] to cause birth defects or other reproductive harm

26 The warning required by paragraph 25 above shall be

prominently affixed to printed on or displayed proximately to

the point-of-sale of each Calcium Product with such

conspicuousness as compared with other words statements

designs or devices on the labeling as to render it likely to be

read and understood by an ordinary individual under customary

conditions of purchase or use If the warning is displayed on

the product container or labeling the warning shall be at least

the same size as the largest of any other health or safety

warnings on the product container or labeling and the word

warning 11 shall be in all capital letters and in bold print If

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 7

1

2

3

4

5

6

7

B

9

lO

11

12

14

1 5

19

20

21

22

23

24

25

26

27

printed on the labeling itself the warning shall be contained in

the same section of the labeling that states other safety

warnings concerning the use of the product The Attorney General

agrees to review any labeling or point of sale signs proposed to

be used under this section and advise the Settling Defendant as

to whether he believes such labeling or point of sale signs

comply with this section The requirement for product labeling

set forth herein is imposed pursuant to the terms of this

Permanent Injunction and is recognized by the parties as not

being the exclusive method of providing a warning under

Proposition 65 and its implementing regulations for the Calcium

Products

27 In the event that the Attorney General determines that

the naturally occurring levels set forth in Table 23 of

paragraph 23 above are higher than the lowest level currently

feasible as stated in 22 CCR section 12501 (a) (4) he shall have

the right to seek a modification of the Permanent Injunction to

reflect the alleged lowest level currently feasible of

naturally occurring lead in the Calcium Products Prior to

seeking such modification the Attorney General shall provide

written notice to the Settling Defendants that he intends to seek

the modification The parties shall have ninety (90) days in

which to confer with the Attorney General concerning the

modification If one or more of the Settling Defendants and the

Attorney General are unable to agree on a modification to the

Permanent Injunction the Attorney General may file a motion with

the court seeking a modification of the Permanent Injunction

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

I AMOUNT 8

1

2

3

4

5

6

7

B

9

10

11 1

12

13

14

l

16

17

18

19

2

2

2

23

24

25

26

2-1

In any motion by the Attorney General seeking such a

modification the burden of producing evidence shall be initially

upon the Attorney General to demonstrate a prima facie case that

the modification sought by the Attorney General is the lowest

level currently feasible The Settling Defendants who do not

agree to such modification retain the ultimate burden of proving

that the modification sought by the Attorney General is lower

than the lowest level currently feasible The parties hereby

agree that the Permanent Injunction should be modified to reflect

any agreement of the parties or any deterrrination by the Court

concerning what is the lowest level currently feasible for lead

in Calcium Products

28 In the event that Settling Defendants individually or

coilectively determine that the naturally occurring levels set

forth in Table 23 of paragraph 23 above are lower than the

lowest level currently feasible as stated in 22 CCR section

1250l(a) (4) such Settling Defendants shall have the right to

seek modification of the Permanent Injunction to reflect the

alleged lowest level currently feasible Prior to seeking such

modification such Settling Defendants shall provide written

notice to the Attorney General that they intend to seek the

modification The parties shall have ninety (90) days in which

to confer concerning the modification If the parties are unable

to agree on a modification to the Permanent Injunction such

Settling Defendants may file a motion with the Court seeking a

modification of the Permanent Injunction In any motion by

Settling Defendants seeking such modification the burden of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 9

1

1

2

3 Ii I

4 j

5 i I

6

7

8

9

10

11

12

L~

14

15

16

17

18

L 3

2J

21

22

23

24

25

26

27

producing evidence and of proof shall be on such Settling

Defendants to prove that the modification sought by the Settling

Defendants is the lowest level currently feasible The parties

hereby agree that the Permanent Injunction should be modified to

reflect any agreement of the parties or any determination by the

Court concerning what is the lowest level currently feasible

I for lead in Calcium Products

29 The term feasible as used in paragraphs 27 and 28

above includes but is not limited to a consideration of the

following factors availability and reliabilityof a supply of

low-lead calcium that meets the requirememts set forth in

paragraphs 22 23 and 24 above cost of low-lead calcium and

resulting increase in manufacturers prices resulting from the

use of the low-lead calcium performance characteristics of lowshy

lead calcium and of the resulting Calcium Product including but

middot not limited to formulation performance safety efficacy and

stability Nothing in this Permanent Injunction shall be

interpreted to require the Settling Defendants to use any calcium

material as an ingredient in a Calcium Product that would render

i their Calcium Product unlawful under state or federal law as

measured by existing andor future applicable California and

federal food and drug laws and regulations Nothing in this

Permanent Injunction shall be interpreted to preclude a Settling

Defendant from advocating for purposes of paragraphs 27 andor

28 that any proposed modification requiring a change in the type

of raw calcium source material as an ingredient in a Calcium

Product is not feasible as defined herein Nothing in this

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 10

ii

I

II I II

I

ii bullI

1

2

middot

4

c

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- ii

8

Permanent Injunction shall be interpreted to preclude the People

from advocating for purposes of paragraphs 2 7 andor 2 8 that

any proposed modification requiring a change in the type of raw

Calcium source material as an ingredient in a calcium product is

feasible as defined herein

9

1 c

1

I

1

I

IIIII

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18

13

2J

21

22

23

~4

25

26

27

I

II

210 Each Settling Defendant shall maintain records

sufficient to establish its compliance with this Permanent

Injunction for a period of four years following the date of

shipment of any Calcium Product into California Such documents

shall be sufficient in detail to establish compliance with the

Protocol set forth in the attached Exhibit A Upon reasonable written notice from the Attorney Generals Office a Settling

Defendant must produce to the Attorney General within ten (10)

tusiness days of the receipt of the Attorney Generals notice

the documents required to be maintained according to this

paragraph To the extent that such documents contain information

which the Settling Defendant maintains is confidential

proprietary andor in the nature of a trade secret (or in fact a

trade secret) and upon written notice as to the asserted

confidential nature of this information by the Settling

Defendant the Attorney General agrees not to disclose this

information to third parties (though the Attorney General may

disclose this information to its attorneys and employees

including professional consultants provided that these persons

also agree to maintain the confidentiality of the information in

these documents) In addition any Settling Defendant may

designate as confidential trade secret information as that term

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 11

1

2

3

4

5

6

7

8

9

~c

2

l~

1 bull C _

~

20

21

22

23

24

25

26

27

is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

11

l

2

3

4

~

6

7

8

9

1

11

12

J3

l 4

17

l 3

~l

~6

shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

21

l

2

3

4

5

6

7

8

9

1G

11

2

3

14

JI

~7

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~9

20

i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

22

23

24 [l

25 II I

26

2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

II al - Ii

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

l

2

3

4

E

7

8 1

9 1

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21

22 1

Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

8

l

1 )

1L

l L

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8

bull =

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22

23

24

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for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

I

IIi

2 1111

31

4 I

) II 11

1~ 11 ii

7 fl

s II 1

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for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

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Its S-~ LIL~~ Pr-ltt-S1J~L

Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

2

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E

C

the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

8

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---

-

6

Its

Dated CONSAC

By

Its

APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

3

Dated

7

8

Dated 7997

l ) AP PROVED AS TO FORM

Dated

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By

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NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

L c

2 l

2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

C

6

7

8

g

0

11

12

15

16

1 7

8

19

21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

lbull9116I 21 11Jl

I

Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

l-litl~ 4ll lUl

Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 8: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

EXHIBIT A

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 1

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON Supervising Deputy Attorney General

EDWARD G WEIL SUSAN S FIERING (State Bar No 121621)

Deputy Attorneys General 2101 Webster Street 12th Floor Oakland CA 94612-3049 Telephone (510) 286-3892

Attorneys for the People

SUPERIOR COURT OF THE STATE OF CALIFORNIA

FOR THE CITY AND COUNTY OF SAN FRANCISCO

PEOPLE OF THE STATE OF CALIFORNIA ex rel DANIELE LUNGREN Attorney)General of the State of California)

Plaintiffs V

WARNER-LAMBERT CO SMITHKLINE BEECHAM CORP AMERICAN HOME PRODUCTS CORP SOURCE NATURAL INC SCHERING-PLOUGH HEALTH CARE PRODUCTS INC PHARMAVITE CORP GENERAL NUTRITION CORP PERRIGO CO TWIN LABORATORIES INC and DOES 1-200

II Defendants i

No 984503

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND FOR PAYMENT OF SETTLEMENT AMOUNT AND ORDER THEREON

5

10

15

20

25

1

2

3

4

6

7

8

9

11

12

13

14

16

17

18

19

21

22

23

24

26

27

Plaintiff the People of the State of California (People)

and defendants Bayer Corporation Johnson amp JohnsonMerck

Consumer Pharmaceuticals Nutrilite a Division of Amway

Corporation and Consac (hereinafter collectively Settling

Defendants) herein enter into this Stipulation for Entry of

Permanent Injunction and for Payment of Settlement Amount

(hereinafter Permanent Injunction) as follows

1 Introduction

11 On February 6 1997 the People of the State of

California ex rel Daniel E Lungren (People) filed a

Complaint for Civil Penalties and Injunctive Relief (Complaint)

in the Superior Court of the State of California City and County

of San Francisco against certain defendants On June 5 1997

the People served the Settling Defendants as Does No 5 through 8

respectively

12 Settling Defendants are companies that employ more

than ten persons and offer for sale within the State of

California one or more of the following calcium-containing

products (hereinafter Calcium Products) which are intended to

be ingested by human beings (a) products containing primarily

calcium that are intended to provide all or a major portion of

the recommended daily allowance of calcium (hereinafter Calcium

Supplements) (b) antacid products containing calcium

(hereinafter Antacids) and (c) dietary supplements as defined

in the federal Dietary Supplements Health and Education Act

Public Law no 103-417 108 Stat 4325 (1994) 21 USC sect

321(ff) containing calcium other than Calcium Supplements or

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION

II AND PAYMENT OF SETTLEMENT AMOUNT 2

1

2

3

4

5

6 I

7

8 I

9

middot

14

15

17

18

19

20

21

22

23

24

Antacids (hereinafter Multiple VitaminsMinerals)

Notwitthstanding any form of packaging of two or more different

alcium Products together the requirements of this Permanent

Injunction shall apply separately to each such different Calcium

froduct The term calcium as used in this Permanent Injunction

means elemental calcium when referring to an amount of calcium

and means any form or salt of calcium when referring to calcium

as an ingredient (active or inactive) in a Calcium Product For purposes of this Permanent Injunction the date of shipment

shall be the date on which the Calcium Product first enters the

stream of commerce except that where a Settling Defendant is

both a manufacturer and a retailer of the Calcium Product date

cf shipment shall mean the date on which a Calcium Product is

transferred from the manufacturing segment of the Settling

Defendants business

13 The Peoples Complaint alleges that Settling

Defendants through the sale of Calcium Products to consumers in

California violated provisions of the Safe Drinking Water and

Toxic Enforcement Act of 1986 Health and Safety Code

sections 252495 et seq (Proposition 65) and Business and

Professions Code sections 1 7200 et seq (Unfair Competition

Act) by knowingly exposing persons to lEiad a chemical known to

the State of California to cause reproductive toxicity without

first providing a clear and reasonable warning to such

25 individuals

14 For purposes of this Permanent Injunction only the

parties stipulate that this Court has jurisdiction over the

26

27

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 3

I

1

2

3

4

5

6

7

8

9

JC

11

16

18

19

2 0

I

21 11

22

23 IiI

24

middot1 25

26

allegations of violations contained in the Complaint and personal

jurisdiction over the Settling Defendants as to the acts alleged

in the Complaint that venue is proper in the City and County of

San Francisco and that this Court has jurisdiction to enter this

Permanent Injunction

15 The parties enter into this Permanent Injunction

pursuant to a settlement of certain disputed claims between the

parties as alleged in the Complaint for the purpose of avoiding

prolonged and costly litigation between the parties hereto By

execution of this Permanent Injunction Settling Defendants

individually and collectively do not admit any facts or

conclusions of law suggesting or demonstrating any violations of

Proposition 65 the Unfair Competition Act or any other

statutory common law or equitable requirements relating to

Calcium Products Nothing in this Permanent Injunction shall be

construed as an admission by Settling Defendants of any fact

issue of law or violation of law nor shall compliance with the

Permanent Injunction constitute or be construed as an admission

by such Settling Defendants of any fact issue of law or

violation of law Nothing in this Permarnmt Injunction shall

prejudice waive or impair any right remedy or defense such

Settling Defendants may have in this or any other or future legal

proceedings However this paragraph shall not diminish or otherwise affect the obligations responsibilities and duties of

such Settling Defendants individually or collectively under

ttis Permanent Injunction

2 Injunctive Relief - Warning Program

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 4 bull

1

2

3

4

S

6

7

8

9

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11

12

13

14

15

16

17

18

19

2 O

21

22

24

25

26

27

21 Where required herein clear and reasonable warning

that use of Calcium Products exposes persons to lead a chemical

known to the State of California to cause birth defects or other

reproductive harm shall be provided by a Settling Defendant in

the manner provided in this Permanent Injunction

22 A Settling Defendant shall provide a warning pursuant

to paragraph 2 5 for each Calcium Product whose date of shipment

is on or after July 1 1997 unless the Settling Defendant can

show pursuant to paragraph 210 and the testing protocol set

forth in Exhibit A attached to this Permanent Injunction that

the Calcium Product causes a total daily exposure to lead of 05

micrograms or less based on the amount of the Calcium Product

supplying a thousand (1000) milligrams of elemental calcium

II excluding any naturally occurring lead in the Calcium Product as

set forth in paragraph 23 below For those Calcium Products

where the recommended or maximum daily dose supplies more than

1500 milligrams of calcium a Settling Defendant shall provide a

I warning unless the Settling Defendant can show pursuant to

paragraph 210 and the testing protocol set forth in attached

i Exhibit A that the recommended daily dose of the Calcium Product

causes a total daily exposure to lead equal to or less than that

set forth in paragraph 24 below

23 A Settling Defendant shall be entitled to exclude from

the calculation of the daily lead exposure caused by a Calcium

Product the amount of lead per 1000 milligrams of calcium as set

forth in Table 23 of this paragraph 23 Compliance with this

Permanent Injunction is established and no warning is required

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 5

1

2

3

4

5

6

7

8

9

10

Jl

12

3

14

1 5

26

under Proposition 65 where the lead exposure caused by an amount

of the Calcium Product supplying 1000 milligrams of calcium does

d not exceed the sum of (a) 05 micrograms of lead per thousand

milligrams of elemental calcium and (b) the amount of lead

excluded on the date of shipment as naturally occurring

pursuant to Table 23 of this paragraph 23 For purposes of

this Permanent Injunction Table 23 of this paragraph 23 sets

forth the amount of lead per 1000 milligrams of elemental calcium

which shall be deemed to be naturally occurring at the lowest

level currently feasible pursuant to Section 12501 of Title 22

cf the California Code of Regulations (CCR) The amounts of

lead and dates set forth in Table 23 shall apply as of the date

of shipment of the Calcium Product

TABLE 2 3

DATE NATURALLY OCCURRING AMOUNT OF LEAD PER 1000 MILLIGRAMS OF CALCIUM

July 1 1997 35 micrograms

April 1 1999 10 microgram

24 Even if no warning is required by paragraphs 22 and

23 above in the event that the recommended daily dose of any

Calcium Product as specified on the label or in any other

package material exceeds 1500 milligrams a Settling Defendant

shall provide a warning pursuant to Propcsition 65 if the total

daily lead exposure from the Calcium Product based on the

recommended daily dose exceeds 150 of the level that would

require a warning pursuant to paragraphs 22 and 23 (based on a

an amount of the Calcium Product supplying 1000 milligrams of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 6

23

27

1

2

3

4

5 J

6

7

8

9

10

11

12

J 8

2 1 1

2 5

27

calcium) above as of the date of shipment of the Calcium Product

For antacids that do not have a recommended daily dose for

purposes of this Permanent Injunction the term recommended

daily dose shall mean two-thirds of the maximum daily dose as

set forth on the label or in any other package material

25 For a Calcium Product that does not meet the standards

set forth in paragraphs 2 2 through 2 4 above a Settling

Defendant shall at the point of manufacture prior to shipment

to California or prior to distribution within California (1)

affix to or print on the Calcium Product container cap label or

unit package or (2) display at the point of sale of the Calcium

Product the following warning (the language in brackets in the

warning below is optional)

WARNING This product contains [lead] a chemical known [to the State of California] to cause birth defects or other reproductive harm

26 The warning required by paragraph 25 above shall be

prominently affixed to printed on or displayed proximately to

the point-of-sale of each Calcium Product with such

conspicuousness as compared with other words statements

designs or devices on the labeling as to render it likely to be

read and understood by an ordinary individual under customary

conditions of purchase or use If the warning is displayed on

the product container or labeling the warning shall be at least

the same size as the largest of any other health or safety

warnings on the product container or labeling and the word

warning 11 shall be in all capital letters and in bold print If

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 7

1

2

3

4

5

6

7

B

9

lO

11

12

14

1 5

19

20

21

22

23

24

25

26

27

printed on the labeling itself the warning shall be contained in

the same section of the labeling that states other safety

warnings concerning the use of the product The Attorney General

agrees to review any labeling or point of sale signs proposed to

be used under this section and advise the Settling Defendant as

to whether he believes such labeling or point of sale signs

comply with this section The requirement for product labeling

set forth herein is imposed pursuant to the terms of this

Permanent Injunction and is recognized by the parties as not

being the exclusive method of providing a warning under

Proposition 65 and its implementing regulations for the Calcium

Products

27 In the event that the Attorney General determines that

the naturally occurring levels set forth in Table 23 of

paragraph 23 above are higher than the lowest level currently

feasible as stated in 22 CCR section 12501 (a) (4) he shall have

the right to seek a modification of the Permanent Injunction to

reflect the alleged lowest level currently feasible of

naturally occurring lead in the Calcium Products Prior to

seeking such modification the Attorney General shall provide

written notice to the Settling Defendants that he intends to seek

the modification The parties shall have ninety (90) days in

which to confer with the Attorney General concerning the

modification If one or more of the Settling Defendants and the

Attorney General are unable to agree on a modification to the

Permanent Injunction the Attorney General may file a motion with

the court seeking a modification of the Permanent Injunction

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

I AMOUNT 8

1

2

3

4

5

6

7

B

9

10

11 1

12

13

14

l

16

17

18

19

2

2

2

23

24

25

26

2-1

In any motion by the Attorney General seeking such a

modification the burden of producing evidence shall be initially

upon the Attorney General to demonstrate a prima facie case that

the modification sought by the Attorney General is the lowest

level currently feasible The Settling Defendants who do not

agree to such modification retain the ultimate burden of proving

that the modification sought by the Attorney General is lower

than the lowest level currently feasible The parties hereby

agree that the Permanent Injunction should be modified to reflect

any agreement of the parties or any deterrrination by the Court

concerning what is the lowest level currently feasible for lead

in Calcium Products

28 In the event that Settling Defendants individually or

coilectively determine that the naturally occurring levels set

forth in Table 23 of paragraph 23 above are lower than the

lowest level currently feasible as stated in 22 CCR section

1250l(a) (4) such Settling Defendants shall have the right to

seek modification of the Permanent Injunction to reflect the

alleged lowest level currently feasible Prior to seeking such

modification such Settling Defendants shall provide written

notice to the Attorney General that they intend to seek the

modification The parties shall have ninety (90) days in which

to confer concerning the modification If the parties are unable

to agree on a modification to the Permanent Injunction such

Settling Defendants may file a motion with the Court seeking a

modification of the Permanent Injunction In any motion by

Settling Defendants seeking such modification the burden of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 9

1

1

2

3 Ii I

4 j

5 i I

6

7

8

9

10

11

12

L~

14

15

16

17

18

L 3

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21

22

23

24

25

26

27

producing evidence and of proof shall be on such Settling

Defendants to prove that the modification sought by the Settling

Defendants is the lowest level currently feasible The parties

hereby agree that the Permanent Injunction should be modified to

reflect any agreement of the parties or any determination by the

Court concerning what is the lowest level currently feasible

I for lead in Calcium Products

29 The term feasible as used in paragraphs 27 and 28

above includes but is not limited to a consideration of the

following factors availability and reliabilityof a supply of

low-lead calcium that meets the requirememts set forth in

paragraphs 22 23 and 24 above cost of low-lead calcium and

resulting increase in manufacturers prices resulting from the

use of the low-lead calcium performance characteristics of lowshy

lead calcium and of the resulting Calcium Product including but

middot not limited to formulation performance safety efficacy and

stability Nothing in this Permanent Injunction shall be

interpreted to require the Settling Defendants to use any calcium

material as an ingredient in a Calcium Product that would render

i their Calcium Product unlawful under state or federal law as

measured by existing andor future applicable California and

federal food and drug laws and regulations Nothing in this

Permanent Injunction shall be interpreted to preclude a Settling

Defendant from advocating for purposes of paragraphs 27 andor

28 that any proposed modification requiring a change in the type

of raw calcium source material as an ingredient in a Calcium

Product is not feasible as defined herein Nothing in this

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 10

ii

I

II I II

I

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1

2

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4

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Permanent Injunction shall be interpreted to preclude the People

from advocating for purposes of paragraphs 2 7 andor 2 8 that

any proposed modification requiring a change in the type of raw

Calcium source material as an ingredient in a calcium product is

feasible as defined herein

9

1 c

1

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21

22

23

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26

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I

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210 Each Settling Defendant shall maintain records

sufficient to establish its compliance with this Permanent

Injunction for a period of four years following the date of

shipment of any Calcium Product into California Such documents

shall be sufficient in detail to establish compliance with the

Protocol set forth in the attached Exhibit A Upon reasonable written notice from the Attorney Generals Office a Settling

Defendant must produce to the Attorney General within ten (10)

tusiness days of the receipt of the Attorney Generals notice

the documents required to be maintained according to this

paragraph To the extent that such documents contain information

which the Settling Defendant maintains is confidential

proprietary andor in the nature of a trade secret (or in fact a

trade secret) and upon written notice as to the asserted

confidential nature of this information by the Settling

Defendant the Attorney General agrees not to disclose this

information to third parties (though the Attorney General may

disclose this information to its attorneys and employees

including professional consultants provided that these persons

also agree to maintain the confidentiality of the information in

these documents) In addition any Settling Defendant may

designate as confidential trade secret information as that term

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 11

1

2

3

4

5

6

7

8

9

~c

2

l~

1 bull C _

~

20

21

22

23

24

25

26

27

is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

11

l

2

3

4

~

6

7

8

9

1

11

12

J3

l 4

17

l 3

~l

~6

shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

21

l

2

3

4

5

6

7

8

9

1G

11

2

3

14

JI

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s

~9

20

i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

22

23

24 [l

25 II I

26

2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

l

2

3

4

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8 1

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22 1

Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

8

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for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

I

IIi

2 1111

31

4 I

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1~ 11 ii

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for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

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Its S-~ LIL~~ Pr-ltt-S1J~L

Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

2

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4

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C

the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

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Its

Dated CONSAC

By

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APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

3

Dated

7

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Dated 7997

l ) AP PROVED AS TO FORM

Dated

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By

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NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

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2 l

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

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6

7

8

g

0

11

12

15

16

1 7

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21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

lbull9116I 21 11Jl

I

Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

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Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 9: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 1

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON Supervising Deputy Attorney General

EDWARD G WEIL SUSAN S FIERING (State Bar No 121621)

Deputy Attorneys General 2101 Webster Street 12th Floor Oakland CA 94612-3049 Telephone (510) 286-3892

Attorneys for the People

SUPERIOR COURT OF THE STATE OF CALIFORNIA

FOR THE CITY AND COUNTY OF SAN FRANCISCO

PEOPLE OF THE STATE OF CALIFORNIA ex rel DANIELE LUNGREN Attorney)General of the State of California)

Plaintiffs V

WARNER-LAMBERT CO SMITHKLINE BEECHAM CORP AMERICAN HOME PRODUCTS CORP SOURCE NATURAL INC SCHERING-PLOUGH HEALTH CARE PRODUCTS INC PHARMAVITE CORP GENERAL NUTRITION CORP PERRIGO CO TWIN LABORATORIES INC and DOES 1-200

II Defendants i

No 984503

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND FOR PAYMENT OF SETTLEMENT AMOUNT AND ORDER THEREON

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25

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Plaintiff the People of the State of California (People)

and defendants Bayer Corporation Johnson amp JohnsonMerck

Consumer Pharmaceuticals Nutrilite a Division of Amway

Corporation and Consac (hereinafter collectively Settling

Defendants) herein enter into this Stipulation for Entry of

Permanent Injunction and for Payment of Settlement Amount

(hereinafter Permanent Injunction) as follows

1 Introduction

11 On February 6 1997 the People of the State of

California ex rel Daniel E Lungren (People) filed a

Complaint for Civil Penalties and Injunctive Relief (Complaint)

in the Superior Court of the State of California City and County

of San Francisco against certain defendants On June 5 1997

the People served the Settling Defendants as Does No 5 through 8

respectively

12 Settling Defendants are companies that employ more

than ten persons and offer for sale within the State of

California one or more of the following calcium-containing

products (hereinafter Calcium Products) which are intended to

be ingested by human beings (a) products containing primarily

calcium that are intended to provide all or a major portion of

the recommended daily allowance of calcium (hereinafter Calcium

Supplements) (b) antacid products containing calcium

(hereinafter Antacids) and (c) dietary supplements as defined

in the federal Dietary Supplements Health and Education Act

Public Law no 103-417 108 Stat 4325 (1994) 21 USC sect

321(ff) containing calcium other than Calcium Supplements or

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION

II AND PAYMENT OF SETTLEMENT AMOUNT 2

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Antacids (hereinafter Multiple VitaminsMinerals)

Notwitthstanding any form of packaging of two or more different

alcium Products together the requirements of this Permanent

Injunction shall apply separately to each such different Calcium

froduct The term calcium as used in this Permanent Injunction

means elemental calcium when referring to an amount of calcium

and means any form or salt of calcium when referring to calcium

as an ingredient (active or inactive) in a Calcium Product For purposes of this Permanent Injunction the date of shipment

shall be the date on which the Calcium Product first enters the

stream of commerce except that where a Settling Defendant is

both a manufacturer and a retailer of the Calcium Product date

cf shipment shall mean the date on which a Calcium Product is

transferred from the manufacturing segment of the Settling

Defendants business

13 The Peoples Complaint alleges that Settling

Defendants through the sale of Calcium Products to consumers in

California violated provisions of the Safe Drinking Water and

Toxic Enforcement Act of 1986 Health and Safety Code

sections 252495 et seq (Proposition 65) and Business and

Professions Code sections 1 7200 et seq (Unfair Competition

Act) by knowingly exposing persons to lEiad a chemical known to

the State of California to cause reproductive toxicity without

first providing a clear and reasonable warning to such

25 individuals

14 For purposes of this Permanent Injunction only the

parties stipulate that this Court has jurisdiction over the

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27

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 3

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allegations of violations contained in the Complaint and personal

jurisdiction over the Settling Defendants as to the acts alleged

in the Complaint that venue is proper in the City and County of

San Francisco and that this Court has jurisdiction to enter this

Permanent Injunction

15 The parties enter into this Permanent Injunction

pursuant to a settlement of certain disputed claims between the

parties as alleged in the Complaint for the purpose of avoiding

prolonged and costly litigation between the parties hereto By

execution of this Permanent Injunction Settling Defendants

individually and collectively do not admit any facts or

conclusions of law suggesting or demonstrating any violations of

Proposition 65 the Unfair Competition Act or any other

statutory common law or equitable requirements relating to

Calcium Products Nothing in this Permanent Injunction shall be

construed as an admission by Settling Defendants of any fact

issue of law or violation of law nor shall compliance with the

Permanent Injunction constitute or be construed as an admission

by such Settling Defendants of any fact issue of law or

violation of law Nothing in this Permarnmt Injunction shall

prejudice waive or impair any right remedy or defense such

Settling Defendants may have in this or any other or future legal

proceedings However this paragraph shall not diminish or otherwise affect the obligations responsibilities and duties of

such Settling Defendants individually or collectively under

ttis Permanent Injunction

2 Injunctive Relief - Warning Program

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 4 bull

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21 Where required herein clear and reasonable warning

that use of Calcium Products exposes persons to lead a chemical

known to the State of California to cause birth defects or other

reproductive harm shall be provided by a Settling Defendant in

the manner provided in this Permanent Injunction

22 A Settling Defendant shall provide a warning pursuant

to paragraph 2 5 for each Calcium Product whose date of shipment

is on or after July 1 1997 unless the Settling Defendant can

show pursuant to paragraph 210 and the testing protocol set

forth in Exhibit A attached to this Permanent Injunction that

the Calcium Product causes a total daily exposure to lead of 05

micrograms or less based on the amount of the Calcium Product

supplying a thousand (1000) milligrams of elemental calcium

II excluding any naturally occurring lead in the Calcium Product as

set forth in paragraph 23 below For those Calcium Products

where the recommended or maximum daily dose supplies more than

1500 milligrams of calcium a Settling Defendant shall provide a

I warning unless the Settling Defendant can show pursuant to

paragraph 210 and the testing protocol set forth in attached

i Exhibit A that the recommended daily dose of the Calcium Product

causes a total daily exposure to lead equal to or less than that

set forth in paragraph 24 below

23 A Settling Defendant shall be entitled to exclude from

the calculation of the daily lead exposure caused by a Calcium

Product the amount of lead per 1000 milligrams of calcium as set

forth in Table 23 of this paragraph 23 Compliance with this

Permanent Injunction is established and no warning is required

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 5

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under Proposition 65 where the lead exposure caused by an amount

of the Calcium Product supplying 1000 milligrams of calcium does

d not exceed the sum of (a) 05 micrograms of lead per thousand

milligrams of elemental calcium and (b) the amount of lead

excluded on the date of shipment as naturally occurring

pursuant to Table 23 of this paragraph 23 For purposes of

this Permanent Injunction Table 23 of this paragraph 23 sets

forth the amount of lead per 1000 milligrams of elemental calcium

which shall be deemed to be naturally occurring at the lowest

level currently feasible pursuant to Section 12501 of Title 22

cf the California Code of Regulations (CCR) The amounts of

lead and dates set forth in Table 23 shall apply as of the date

of shipment of the Calcium Product

TABLE 2 3

DATE NATURALLY OCCURRING AMOUNT OF LEAD PER 1000 MILLIGRAMS OF CALCIUM

July 1 1997 35 micrograms

April 1 1999 10 microgram

24 Even if no warning is required by paragraphs 22 and

23 above in the event that the recommended daily dose of any

Calcium Product as specified on the label or in any other

package material exceeds 1500 milligrams a Settling Defendant

shall provide a warning pursuant to Propcsition 65 if the total

daily lead exposure from the Calcium Product based on the

recommended daily dose exceeds 150 of the level that would

require a warning pursuant to paragraphs 22 and 23 (based on a

an amount of the Calcium Product supplying 1000 milligrams of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 6

23

27

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calcium) above as of the date of shipment of the Calcium Product

For antacids that do not have a recommended daily dose for

purposes of this Permanent Injunction the term recommended

daily dose shall mean two-thirds of the maximum daily dose as

set forth on the label or in any other package material

25 For a Calcium Product that does not meet the standards

set forth in paragraphs 2 2 through 2 4 above a Settling

Defendant shall at the point of manufacture prior to shipment

to California or prior to distribution within California (1)

affix to or print on the Calcium Product container cap label or

unit package or (2) display at the point of sale of the Calcium

Product the following warning (the language in brackets in the

warning below is optional)

WARNING This product contains [lead] a chemical known [to the State of California] to cause birth defects or other reproductive harm

26 The warning required by paragraph 25 above shall be

prominently affixed to printed on or displayed proximately to

the point-of-sale of each Calcium Product with such

conspicuousness as compared with other words statements

designs or devices on the labeling as to render it likely to be

read and understood by an ordinary individual under customary

conditions of purchase or use If the warning is displayed on

the product container or labeling the warning shall be at least

the same size as the largest of any other health or safety

warnings on the product container or labeling and the word

warning 11 shall be in all capital letters and in bold print If

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 7

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printed on the labeling itself the warning shall be contained in

the same section of the labeling that states other safety

warnings concerning the use of the product The Attorney General

agrees to review any labeling or point of sale signs proposed to

be used under this section and advise the Settling Defendant as

to whether he believes such labeling or point of sale signs

comply with this section The requirement for product labeling

set forth herein is imposed pursuant to the terms of this

Permanent Injunction and is recognized by the parties as not

being the exclusive method of providing a warning under

Proposition 65 and its implementing regulations for the Calcium

Products

27 In the event that the Attorney General determines that

the naturally occurring levels set forth in Table 23 of

paragraph 23 above are higher than the lowest level currently

feasible as stated in 22 CCR section 12501 (a) (4) he shall have

the right to seek a modification of the Permanent Injunction to

reflect the alleged lowest level currently feasible of

naturally occurring lead in the Calcium Products Prior to

seeking such modification the Attorney General shall provide

written notice to the Settling Defendants that he intends to seek

the modification The parties shall have ninety (90) days in

which to confer with the Attorney General concerning the

modification If one or more of the Settling Defendants and the

Attorney General are unable to agree on a modification to the

Permanent Injunction the Attorney General may file a motion with

the court seeking a modification of the Permanent Injunction

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

I AMOUNT 8

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In any motion by the Attorney General seeking such a

modification the burden of producing evidence shall be initially

upon the Attorney General to demonstrate a prima facie case that

the modification sought by the Attorney General is the lowest

level currently feasible The Settling Defendants who do not

agree to such modification retain the ultimate burden of proving

that the modification sought by the Attorney General is lower

than the lowest level currently feasible The parties hereby

agree that the Permanent Injunction should be modified to reflect

any agreement of the parties or any deterrrination by the Court

concerning what is the lowest level currently feasible for lead

in Calcium Products

28 In the event that Settling Defendants individually or

coilectively determine that the naturally occurring levels set

forth in Table 23 of paragraph 23 above are lower than the

lowest level currently feasible as stated in 22 CCR section

1250l(a) (4) such Settling Defendants shall have the right to

seek modification of the Permanent Injunction to reflect the

alleged lowest level currently feasible Prior to seeking such

modification such Settling Defendants shall provide written

notice to the Attorney General that they intend to seek the

modification The parties shall have ninety (90) days in which

to confer concerning the modification If the parties are unable

to agree on a modification to the Permanent Injunction such

Settling Defendants may file a motion with the Court seeking a

modification of the Permanent Injunction In any motion by

Settling Defendants seeking such modification the burden of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 9

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producing evidence and of proof shall be on such Settling

Defendants to prove that the modification sought by the Settling

Defendants is the lowest level currently feasible The parties

hereby agree that the Permanent Injunction should be modified to

reflect any agreement of the parties or any determination by the

Court concerning what is the lowest level currently feasible

I for lead in Calcium Products

29 The term feasible as used in paragraphs 27 and 28

above includes but is not limited to a consideration of the

following factors availability and reliabilityof a supply of

low-lead calcium that meets the requirememts set forth in

paragraphs 22 23 and 24 above cost of low-lead calcium and

resulting increase in manufacturers prices resulting from the

use of the low-lead calcium performance characteristics of lowshy

lead calcium and of the resulting Calcium Product including but

middot not limited to formulation performance safety efficacy and

stability Nothing in this Permanent Injunction shall be

interpreted to require the Settling Defendants to use any calcium

material as an ingredient in a Calcium Product that would render

i their Calcium Product unlawful under state or federal law as

measured by existing andor future applicable California and

federal food and drug laws and regulations Nothing in this

Permanent Injunction shall be interpreted to preclude a Settling

Defendant from advocating for purposes of paragraphs 27 andor

28 that any proposed modification requiring a change in the type

of raw calcium source material as an ingredient in a Calcium

Product is not feasible as defined herein Nothing in this

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 10

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Permanent Injunction shall be interpreted to preclude the People

from advocating for purposes of paragraphs 2 7 andor 2 8 that

any proposed modification requiring a change in the type of raw

Calcium source material as an ingredient in a calcium product is

feasible as defined herein

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210 Each Settling Defendant shall maintain records

sufficient to establish its compliance with this Permanent

Injunction for a period of four years following the date of

shipment of any Calcium Product into California Such documents

shall be sufficient in detail to establish compliance with the

Protocol set forth in the attached Exhibit A Upon reasonable written notice from the Attorney Generals Office a Settling

Defendant must produce to the Attorney General within ten (10)

tusiness days of the receipt of the Attorney Generals notice

the documents required to be maintained according to this

paragraph To the extent that such documents contain information

which the Settling Defendant maintains is confidential

proprietary andor in the nature of a trade secret (or in fact a

trade secret) and upon written notice as to the asserted

confidential nature of this information by the Settling

Defendant the Attorney General agrees not to disclose this

information to third parties (though the Attorney General may

disclose this information to its attorneys and employees

including professional consultants provided that these persons

also agree to maintain the confidentiality of the information in

these documents) In addition any Settling Defendant may

designate as confidential trade secret information as that term

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 11

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is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

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shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

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2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

l

2

3

4

E

7

8 1

9 1

c I

~l

~t

_

2)

21

22 1

Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

8

l

1 )

1L

l L

l

- C

8

bull =

)()

) I

22

23

24

25

26

27

i I

ii

for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

I

IIi

2 1111

31

4 I

) II 11

1~ 11 ii

7 fl

s II 1

g 1 I

l )

for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

middotJC-~ J 14~ LJ - ---lt__

Its S-~ LIL~~ Pr-ltt-S1J~L

Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

2

~ li

4

5 middot

E

E

C

the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

8

_ _

---

-

6

Its

Dated CONSAC

By

Its

APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

3

Dated

7

8

Dated 7997

l ) AP PROVED AS TO FORM

Dated

l -~

~ IS SO ORDERED

By

Its

NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

L c

2 l

2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

C

6

7

8

g

0

11

12

15

16

1 7

8

19

21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

lbull9116I 21 11Jl

I

Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

l-litl~ 4ll lUl

Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 10: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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Plaintiff the People of the State of California (People)

and defendants Bayer Corporation Johnson amp JohnsonMerck

Consumer Pharmaceuticals Nutrilite a Division of Amway

Corporation and Consac (hereinafter collectively Settling

Defendants) herein enter into this Stipulation for Entry of

Permanent Injunction and for Payment of Settlement Amount

(hereinafter Permanent Injunction) as follows

1 Introduction

11 On February 6 1997 the People of the State of

California ex rel Daniel E Lungren (People) filed a

Complaint for Civil Penalties and Injunctive Relief (Complaint)

in the Superior Court of the State of California City and County

of San Francisco against certain defendants On June 5 1997

the People served the Settling Defendants as Does No 5 through 8

respectively

12 Settling Defendants are companies that employ more

than ten persons and offer for sale within the State of

California one or more of the following calcium-containing

products (hereinafter Calcium Products) which are intended to

be ingested by human beings (a) products containing primarily

calcium that are intended to provide all or a major portion of

the recommended daily allowance of calcium (hereinafter Calcium

Supplements) (b) antacid products containing calcium

(hereinafter Antacids) and (c) dietary supplements as defined

in the federal Dietary Supplements Health and Education Act

Public Law no 103-417 108 Stat 4325 (1994) 21 USC sect

321(ff) containing calcium other than Calcium Supplements or

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION

II AND PAYMENT OF SETTLEMENT AMOUNT 2

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Antacids (hereinafter Multiple VitaminsMinerals)

Notwitthstanding any form of packaging of two or more different

alcium Products together the requirements of this Permanent

Injunction shall apply separately to each such different Calcium

froduct The term calcium as used in this Permanent Injunction

means elemental calcium when referring to an amount of calcium

and means any form or salt of calcium when referring to calcium

as an ingredient (active or inactive) in a Calcium Product For purposes of this Permanent Injunction the date of shipment

shall be the date on which the Calcium Product first enters the

stream of commerce except that where a Settling Defendant is

both a manufacturer and a retailer of the Calcium Product date

cf shipment shall mean the date on which a Calcium Product is

transferred from the manufacturing segment of the Settling

Defendants business

13 The Peoples Complaint alleges that Settling

Defendants through the sale of Calcium Products to consumers in

California violated provisions of the Safe Drinking Water and

Toxic Enforcement Act of 1986 Health and Safety Code

sections 252495 et seq (Proposition 65) and Business and

Professions Code sections 1 7200 et seq (Unfair Competition

Act) by knowingly exposing persons to lEiad a chemical known to

the State of California to cause reproductive toxicity without

first providing a clear and reasonable warning to such

25 individuals

14 For purposes of this Permanent Injunction only the

parties stipulate that this Court has jurisdiction over the

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27

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 3

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allegations of violations contained in the Complaint and personal

jurisdiction over the Settling Defendants as to the acts alleged

in the Complaint that venue is proper in the City and County of

San Francisco and that this Court has jurisdiction to enter this

Permanent Injunction

15 The parties enter into this Permanent Injunction

pursuant to a settlement of certain disputed claims between the

parties as alleged in the Complaint for the purpose of avoiding

prolonged and costly litigation between the parties hereto By

execution of this Permanent Injunction Settling Defendants

individually and collectively do not admit any facts or

conclusions of law suggesting or demonstrating any violations of

Proposition 65 the Unfair Competition Act or any other

statutory common law or equitable requirements relating to

Calcium Products Nothing in this Permanent Injunction shall be

construed as an admission by Settling Defendants of any fact

issue of law or violation of law nor shall compliance with the

Permanent Injunction constitute or be construed as an admission

by such Settling Defendants of any fact issue of law or

violation of law Nothing in this Permarnmt Injunction shall

prejudice waive or impair any right remedy or defense such

Settling Defendants may have in this or any other or future legal

proceedings However this paragraph shall not diminish or otherwise affect the obligations responsibilities and duties of

such Settling Defendants individually or collectively under

ttis Permanent Injunction

2 Injunctive Relief - Warning Program

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 4 bull

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21 Where required herein clear and reasonable warning

that use of Calcium Products exposes persons to lead a chemical

known to the State of California to cause birth defects or other

reproductive harm shall be provided by a Settling Defendant in

the manner provided in this Permanent Injunction

22 A Settling Defendant shall provide a warning pursuant

to paragraph 2 5 for each Calcium Product whose date of shipment

is on or after July 1 1997 unless the Settling Defendant can

show pursuant to paragraph 210 and the testing protocol set

forth in Exhibit A attached to this Permanent Injunction that

the Calcium Product causes a total daily exposure to lead of 05

micrograms or less based on the amount of the Calcium Product

supplying a thousand (1000) milligrams of elemental calcium

II excluding any naturally occurring lead in the Calcium Product as

set forth in paragraph 23 below For those Calcium Products

where the recommended or maximum daily dose supplies more than

1500 milligrams of calcium a Settling Defendant shall provide a

I warning unless the Settling Defendant can show pursuant to

paragraph 210 and the testing protocol set forth in attached

i Exhibit A that the recommended daily dose of the Calcium Product

causes a total daily exposure to lead equal to or less than that

set forth in paragraph 24 below

23 A Settling Defendant shall be entitled to exclude from

the calculation of the daily lead exposure caused by a Calcium

Product the amount of lead per 1000 milligrams of calcium as set

forth in Table 23 of this paragraph 23 Compliance with this

Permanent Injunction is established and no warning is required

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 5

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under Proposition 65 where the lead exposure caused by an amount

of the Calcium Product supplying 1000 milligrams of calcium does

d not exceed the sum of (a) 05 micrograms of lead per thousand

milligrams of elemental calcium and (b) the amount of lead

excluded on the date of shipment as naturally occurring

pursuant to Table 23 of this paragraph 23 For purposes of

this Permanent Injunction Table 23 of this paragraph 23 sets

forth the amount of lead per 1000 milligrams of elemental calcium

which shall be deemed to be naturally occurring at the lowest

level currently feasible pursuant to Section 12501 of Title 22

cf the California Code of Regulations (CCR) The amounts of

lead and dates set forth in Table 23 shall apply as of the date

of shipment of the Calcium Product

TABLE 2 3

DATE NATURALLY OCCURRING AMOUNT OF LEAD PER 1000 MILLIGRAMS OF CALCIUM

July 1 1997 35 micrograms

April 1 1999 10 microgram

24 Even if no warning is required by paragraphs 22 and

23 above in the event that the recommended daily dose of any

Calcium Product as specified on the label or in any other

package material exceeds 1500 milligrams a Settling Defendant

shall provide a warning pursuant to Propcsition 65 if the total

daily lead exposure from the Calcium Product based on the

recommended daily dose exceeds 150 of the level that would

require a warning pursuant to paragraphs 22 and 23 (based on a

an amount of the Calcium Product supplying 1000 milligrams of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 6

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calcium) above as of the date of shipment of the Calcium Product

For antacids that do not have a recommended daily dose for

purposes of this Permanent Injunction the term recommended

daily dose shall mean two-thirds of the maximum daily dose as

set forth on the label or in any other package material

25 For a Calcium Product that does not meet the standards

set forth in paragraphs 2 2 through 2 4 above a Settling

Defendant shall at the point of manufacture prior to shipment

to California or prior to distribution within California (1)

affix to or print on the Calcium Product container cap label or

unit package or (2) display at the point of sale of the Calcium

Product the following warning (the language in brackets in the

warning below is optional)

WARNING This product contains [lead] a chemical known [to the State of California] to cause birth defects or other reproductive harm

26 The warning required by paragraph 25 above shall be

prominently affixed to printed on or displayed proximately to

the point-of-sale of each Calcium Product with such

conspicuousness as compared with other words statements

designs or devices on the labeling as to render it likely to be

read and understood by an ordinary individual under customary

conditions of purchase or use If the warning is displayed on

the product container or labeling the warning shall be at least

the same size as the largest of any other health or safety

warnings on the product container or labeling and the word

warning 11 shall be in all capital letters and in bold print If

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printed on the labeling itself the warning shall be contained in

the same section of the labeling that states other safety

warnings concerning the use of the product The Attorney General

agrees to review any labeling or point of sale signs proposed to

be used under this section and advise the Settling Defendant as

to whether he believes such labeling or point of sale signs

comply with this section The requirement for product labeling

set forth herein is imposed pursuant to the terms of this

Permanent Injunction and is recognized by the parties as not

being the exclusive method of providing a warning under

Proposition 65 and its implementing regulations for the Calcium

Products

27 In the event that the Attorney General determines that

the naturally occurring levels set forth in Table 23 of

paragraph 23 above are higher than the lowest level currently

feasible as stated in 22 CCR section 12501 (a) (4) he shall have

the right to seek a modification of the Permanent Injunction to

reflect the alleged lowest level currently feasible of

naturally occurring lead in the Calcium Products Prior to

seeking such modification the Attorney General shall provide

written notice to the Settling Defendants that he intends to seek

the modification The parties shall have ninety (90) days in

which to confer with the Attorney General concerning the

modification If one or more of the Settling Defendants and the

Attorney General are unable to agree on a modification to the

Permanent Injunction the Attorney General may file a motion with

the court seeking a modification of the Permanent Injunction

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

I AMOUNT 8

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In any motion by the Attorney General seeking such a

modification the burden of producing evidence shall be initially

upon the Attorney General to demonstrate a prima facie case that

the modification sought by the Attorney General is the lowest

level currently feasible The Settling Defendants who do not

agree to such modification retain the ultimate burden of proving

that the modification sought by the Attorney General is lower

than the lowest level currently feasible The parties hereby

agree that the Permanent Injunction should be modified to reflect

any agreement of the parties or any deterrrination by the Court

concerning what is the lowest level currently feasible for lead

in Calcium Products

28 In the event that Settling Defendants individually or

coilectively determine that the naturally occurring levels set

forth in Table 23 of paragraph 23 above are lower than the

lowest level currently feasible as stated in 22 CCR section

1250l(a) (4) such Settling Defendants shall have the right to

seek modification of the Permanent Injunction to reflect the

alleged lowest level currently feasible Prior to seeking such

modification such Settling Defendants shall provide written

notice to the Attorney General that they intend to seek the

modification The parties shall have ninety (90) days in which

to confer concerning the modification If the parties are unable

to agree on a modification to the Permanent Injunction such

Settling Defendants may file a motion with the Court seeking a

modification of the Permanent Injunction In any motion by

Settling Defendants seeking such modification the burden of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 9

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producing evidence and of proof shall be on such Settling

Defendants to prove that the modification sought by the Settling

Defendants is the lowest level currently feasible The parties

hereby agree that the Permanent Injunction should be modified to

reflect any agreement of the parties or any determination by the

Court concerning what is the lowest level currently feasible

I for lead in Calcium Products

29 The term feasible as used in paragraphs 27 and 28

above includes but is not limited to a consideration of the

following factors availability and reliabilityof a supply of

low-lead calcium that meets the requirememts set forth in

paragraphs 22 23 and 24 above cost of low-lead calcium and

resulting increase in manufacturers prices resulting from the

use of the low-lead calcium performance characteristics of lowshy

lead calcium and of the resulting Calcium Product including but

middot not limited to formulation performance safety efficacy and

stability Nothing in this Permanent Injunction shall be

interpreted to require the Settling Defendants to use any calcium

material as an ingredient in a Calcium Product that would render

i their Calcium Product unlawful under state or federal law as

measured by existing andor future applicable California and

federal food and drug laws and regulations Nothing in this

Permanent Injunction shall be interpreted to preclude a Settling

Defendant from advocating for purposes of paragraphs 27 andor

28 that any proposed modification requiring a change in the type

of raw calcium source material as an ingredient in a Calcium

Product is not feasible as defined herein Nothing in this

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 10

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Permanent Injunction shall be interpreted to preclude the People

from advocating for purposes of paragraphs 2 7 andor 2 8 that

any proposed modification requiring a change in the type of raw

Calcium source material as an ingredient in a calcium product is

feasible as defined herein

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210 Each Settling Defendant shall maintain records

sufficient to establish its compliance with this Permanent

Injunction for a period of four years following the date of

shipment of any Calcium Product into California Such documents

shall be sufficient in detail to establish compliance with the

Protocol set forth in the attached Exhibit A Upon reasonable written notice from the Attorney Generals Office a Settling

Defendant must produce to the Attorney General within ten (10)

tusiness days of the receipt of the Attorney Generals notice

the documents required to be maintained according to this

paragraph To the extent that such documents contain information

which the Settling Defendant maintains is confidential

proprietary andor in the nature of a trade secret (or in fact a

trade secret) and upon written notice as to the asserted

confidential nature of this information by the Settling

Defendant the Attorney General agrees not to disclose this

information to third parties (though the Attorney General may

disclose this information to its attorneys and employees

including professional consultants provided that these persons

also agree to maintain the confidentiality of the information in

these documents) In addition any Settling Defendant may

designate as confidential trade secret information as that term

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 11

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is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

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shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

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2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

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Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

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for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

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31

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for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

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Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

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STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

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the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

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Dated CONSAC

By

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APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

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STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

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Dated

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NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

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6

7

8

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0

11

12

15

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Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

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APPROVED AS TO FORMDatedn 17 1997

By

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IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

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Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

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Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

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Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

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Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

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    • EXHIBIT A
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Page 11: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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Antacids (hereinafter Multiple VitaminsMinerals)

Notwitthstanding any form of packaging of two or more different

alcium Products together the requirements of this Permanent

Injunction shall apply separately to each such different Calcium

froduct The term calcium as used in this Permanent Injunction

means elemental calcium when referring to an amount of calcium

and means any form or salt of calcium when referring to calcium

as an ingredient (active or inactive) in a Calcium Product For purposes of this Permanent Injunction the date of shipment

shall be the date on which the Calcium Product first enters the

stream of commerce except that where a Settling Defendant is

both a manufacturer and a retailer of the Calcium Product date

cf shipment shall mean the date on which a Calcium Product is

transferred from the manufacturing segment of the Settling

Defendants business

13 The Peoples Complaint alleges that Settling

Defendants through the sale of Calcium Products to consumers in

California violated provisions of the Safe Drinking Water and

Toxic Enforcement Act of 1986 Health and Safety Code

sections 252495 et seq (Proposition 65) and Business and

Professions Code sections 1 7200 et seq (Unfair Competition

Act) by knowingly exposing persons to lEiad a chemical known to

the State of California to cause reproductive toxicity without

first providing a clear and reasonable warning to such

25 individuals

14 For purposes of this Permanent Injunction only the

parties stipulate that this Court has jurisdiction over the

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 3

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allegations of violations contained in the Complaint and personal

jurisdiction over the Settling Defendants as to the acts alleged

in the Complaint that venue is proper in the City and County of

San Francisco and that this Court has jurisdiction to enter this

Permanent Injunction

15 The parties enter into this Permanent Injunction

pursuant to a settlement of certain disputed claims between the

parties as alleged in the Complaint for the purpose of avoiding

prolonged and costly litigation between the parties hereto By

execution of this Permanent Injunction Settling Defendants

individually and collectively do not admit any facts or

conclusions of law suggesting or demonstrating any violations of

Proposition 65 the Unfair Competition Act or any other

statutory common law or equitable requirements relating to

Calcium Products Nothing in this Permanent Injunction shall be

construed as an admission by Settling Defendants of any fact

issue of law or violation of law nor shall compliance with the

Permanent Injunction constitute or be construed as an admission

by such Settling Defendants of any fact issue of law or

violation of law Nothing in this Permarnmt Injunction shall

prejudice waive or impair any right remedy or defense such

Settling Defendants may have in this or any other or future legal

proceedings However this paragraph shall not diminish or otherwise affect the obligations responsibilities and duties of

such Settling Defendants individually or collectively under

ttis Permanent Injunction

2 Injunctive Relief - Warning Program

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 4 bull

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21 Where required herein clear and reasonable warning

that use of Calcium Products exposes persons to lead a chemical

known to the State of California to cause birth defects or other

reproductive harm shall be provided by a Settling Defendant in

the manner provided in this Permanent Injunction

22 A Settling Defendant shall provide a warning pursuant

to paragraph 2 5 for each Calcium Product whose date of shipment

is on or after July 1 1997 unless the Settling Defendant can

show pursuant to paragraph 210 and the testing protocol set

forth in Exhibit A attached to this Permanent Injunction that

the Calcium Product causes a total daily exposure to lead of 05

micrograms or less based on the amount of the Calcium Product

supplying a thousand (1000) milligrams of elemental calcium

II excluding any naturally occurring lead in the Calcium Product as

set forth in paragraph 23 below For those Calcium Products

where the recommended or maximum daily dose supplies more than

1500 milligrams of calcium a Settling Defendant shall provide a

I warning unless the Settling Defendant can show pursuant to

paragraph 210 and the testing protocol set forth in attached

i Exhibit A that the recommended daily dose of the Calcium Product

causes a total daily exposure to lead equal to or less than that

set forth in paragraph 24 below

23 A Settling Defendant shall be entitled to exclude from

the calculation of the daily lead exposure caused by a Calcium

Product the amount of lead per 1000 milligrams of calcium as set

forth in Table 23 of this paragraph 23 Compliance with this

Permanent Injunction is established and no warning is required

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 5

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under Proposition 65 where the lead exposure caused by an amount

of the Calcium Product supplying 1000 milligrams of calcium does

d not exceed the sum of (a) 05 micrograms of lead per thousand

milligrams of elemental calcium and (b) the amount of lead

excluded on the date of shipment as naturally occurring

pursuant to Table 23 of this paragraph 23 For purposes of

this Permanent Injunction Table 23 of this paragraph 23 sets

forth the amount of lead per 1000 milligrams of elemental calcium

which shall be deemed to be naturally occurring at the lowest

level currently feasible pursuant to Section 12501 of Title 22

cf the California Code of Regulations (CCR) The amounts of

lead and dates set forth in Table 23 shall apply as of the date

of shipment of the Calcium Product

TABLE 2 3

DATE NATURALLY OCCURRING AMOUNT OF LEAD PER 1000 MILLIGRAMS OF CALCIUM

July 1 1997 35 micrograms

April 1 1999 10 microgram

24 Even if no warning is required by paragraphs 22 and

23 above in the event that the recommended daily dose of any

Calcium Product as specified on the label or in any other

package material exceeds 1500 milligrams a Settling Defendant

shall provide a warning pursuant to Propcsition 65 if the total

daily lead exposure from the Calcium Product based on the

recommended daily dose exceeds 150 of the level that would

require a warning pursuant to paragraphs 22 and 23 (based on a

an amount of the Calcium Product supplying 1000 milligrams of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 6

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calcium) above as of the date of shipment of the Calcium Product

For antacids that do not have a recommended daily dose for

purposes of this Permanent Injunction the term recommended

daily dose shall mean two-thirds of the maximum daily dose as

set forth on the label or in any other package material

25 For a Calcium Product that does not meet the standards

set forth in paragraphs 2 2 through 2 4 above a Settling

Defendant shall at the point of manufacture prior to shipment

to California or prior to distribution within California (1)

affix to or print on the Calcium Product container cap label or

unit package or (2) display at the point of sale of the Calcium

Product the following warning (the language in brackets in the

warning below is optional)

WARNING This product contains [lead] a chemical known [to the State of California] to cause birth defects or other reproductive harm

26 The warning required by paragraph 25 above shall be

prominently affixed to printed on or displayed proximately to

the point-of-sale of each Calcium Product with such

conspicuousness as compared with other words statements

designs or devices on the labeling as to render it likely to be

read and understood by an ordinary individual under customary

conditions of purchase or use If the warning is displayed on

the product container or labeling the warning shall be at least

the same size as the largest of any other health or safety

warnings on the product container or labeling and the word

warning 11 shall be in all capital letters and in bold print If

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 7

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printed on the labeling itself the warning shall be contained in

the same section of the labeling that states other safety

warnings concerning the use of the product The Attorney General

agrees to review any labeling or point of sale signs proposed to

be used under this section and advise the Settling Defendant as

to whether he believes such labeling or point of sale signs

comply with this section The requirement for product labeling

set forth herein is imposed pursuant to the terms of this

Permanent Injunction and is recognized by the parties as not

being the exclusive method of providing a warning under

Proposition 65 and its implementing regulations for the Calcium

Products

27 In the event that the Attorney General determines that

the naturally occurring levels set forth in Table 23 of

paragraph 23 above are higher than the lowest level currently

feasible as stated in 22 CCR section 12501 (a) (4) he shall have

the right to seek a modification of the Permanent Injunction to

reflect the alleged lowest level currently feasible of

naturally occurring lead in the Calcium Products Prior to

seeking such modification the Attorney General shall provide

written notice to the Settling Defendants that he intends to seek

the modification The parties shall have ninety (90) days in

which to confer with the Attorney General concerning the

modification If one or more of the Settling Defendants and the

Attorney General are unable to agree on a modification to the

Permanent Injunction the Attorney General may file a motion with

the court seeking a modification of the Permanent Injunction

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

I AMOUNT 8

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In any motion by the Attorney General seeking such a

modification the burden of producing evidence shall be initially

upon the Attorney General to demonstrate a prima facie case that

the modification sought by the Attorney General is the lowest

level currently feasible The Settling Defendants who do not

agree to such modification retain the ultimate burden of proving

that the modification sought by the Attorney General is lower

than the lowest level currently feasible The parties hereby

agree that the Permanent Injunction should be modified to reflect

any agreement of the parties or any deterrrination by the Court

concerning what is the lowest level currently feasible for lead

in Calcium Products

28 In the event that Settling Defendants individually or

coilectively determine that the naturally occurring levels set

forth in Table 23 of paragraph 23 above are lower than the

lowest level currently feasible as stated in 22 CCR section

1250l(a) (4) such Settling Defendants shall have the right to

seek modification of the Permanent Injunction to reflect the

alleged lowest level currently feasible Prior to seeking such

modification such Settling Defendants shall provide written

notice to the Attorney General that they intend to seek the

modification The parties shall have ninety (90) days in which

to confer concerning the modification If the parties are unable

to agree on a modification to the Permanent Injunction such

Settling Defendants may file a motion with the Court seeking a

modification of the Permanent Injunction In any motion by

Settling Defendants seeking such modification the burden of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 9

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producing evidence and of proof shall be on such Settling

Defendants to prove that the modification sought by the Settling

Defendants is the lowest level currently feasible The parties

hereby agree that the Permanent Injunction should be modified to

reflect any agreement of the parties or any determination by the

Court concerning what is the lowest level currently feasible

I for lead in Calcium Products

29 The term feasible as used in paragraphs 27 and 28

above includes but is not limited to a consideration of the

following factors availability and reliabilityof a supply of

low-lead calcium that meets the requirememts set forth in

paragraphs 22 23 and 24 above cost of low-lead calcium and

resulting increase in manufacturers prices resulting from the

use of the low-lead calcium performance characteristics of lowshy

lead calcium and of the resulting Calcium Product including but

middot not limited to formulation performance safety efficacy and

stability Nothing in this Permanent Injunction shall be

interpreted to require the Settling Defendants to use any calcium

material as an ingredient in a Calcium Product that would render

i their Calcium Product unlawful under state or federal law as

measured by existing andor future applicable California and

federal food and drug laws and regulations Nothing in this

Permanent Injunction shall be interpreted to preclude a Settling

Defendant from advocating for purposes of paragraphs 27 andor

28 that any proposed modification requiring a change in the type

of raw calcium source material as an ingredient in a Calcium

Product is not feasible as defined herein Nothing in this

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 10

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Permanent Injunction shall be interpreted to preclude the People

from advocating for purposes of paragraphs 2 7 andor 2 8 that

any proposed modification requiring a change in the type of raw

Calcium source material as an ingredient in a calcium product is

feasible as defined herein

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210 Each Settling Defendant shall maintain records

sufficient to establish its compliance with this Permanent

Injunction for a period of four years following the date of

shipment of any Calcium Product into California Such documents

shall be sufficient in detail to establish compliance with the

Protocol set forth in the attached Exhibit A Upon reasonable written notice from the Attorney Generals Office a Settling

Defendant must produce to the Attorney General within ten (10)

tusiness days of the receipt of the Attorney Generals notice

the documents required to be maintained according to this

paragraph To the extent that such documents contain information

which the Settling Defendant maintains is confidential

proprietary andor in the nature of a trade secret (or in fact a

trade secret) and upon written notice as to the asserted

confidential nature of this information by the Settling

Defendant the Attorney General agrees not to disclose this

information to third parties (though the Attorney General may

disclose this information to its attorneys and employees

including professional consultants provided that these persons

also agree to maintain the confidentiality of the information in

these documents) In addition any Settling Defendant may

designate as confidential trade secret information as that term

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 11

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is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

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shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

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People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

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Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

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for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

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for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

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Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

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STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

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the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

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Dated CONSAC

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APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

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STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

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NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

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Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

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APPROVED AS TO FORMDatedn 17 1997

By

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IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

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Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

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22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

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Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

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23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

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24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

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252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

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Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

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33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

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E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

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313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

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315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

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preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

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Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 12: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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allegations of violations contained in the Complaint and personal

jurisdiction over the Settling Defendants as to the acts alleged

in the Complaint that venue is proper in the City and County of

San Francisco and that this Court has jurisdiction to enter this

Permanent Injunction

15 The parties enter into this Permanent Injunction

pursuant to a settlement of certain disputed claims between the

parties as alleged in the Complaint for the purpose of avoiding

prolonged and costly litigation between the parties hereto By

execution of this Permanent Injunction Settling Defendants

individually and collectively do not admit any facts or

conclusions of law suggesting or demonstrating any violations of

Proposition 65 the Unfair Competition Act or any other

statutory common law or equitable requirements relating to

Calcium Products Nothing in this Permanent Injunction shall be

construed as an admission by Settling Defendants of any fact

issue of law or violation of law nor shall compliance with the

Permanent Injunction constitute or be construed as an admission

by such Settling Defendants of any fact issue of law or

violation of law Nothing in this Permarnmt Injunction shall

prejudice waive or impair any right remedy or defense such

Settling Defendants may have in this or any other or future legal

proceedings However this paragraph shall not diminish or otherwise affect the obligations responsibilities and duties of

such Settling Defendants individually or collectively under

ttis Permanent Injunction

2 Injunctive Relief - Warning Program

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 4 bull

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21 Where required herein clear and reasonable warning

that use of Calcium Products exposes persons to lead a chemical

known to the State of California to cause birth defects or other

reproductive harm shall be provided by a Settling Defendant in

the manner provided in this Permanent Injunction

22 A Settling Defendant shall provide a warning pursuant

to paragraph 2 5 for each Calcium Product whose date of shipment

is on or after July 1 1997 unless the Settling Defendant can

show pursuant to paragraph 210 and the testing protocol set

forth in Exhibit A attached to this Permanent Injunction that

the Calcium Product causes a total daily exposure to lead of 05

micrograms or less based on the amount of the Calcium Product

supplying a thousand (1000) milligrams of elemental calcium

II excluding any naturally occurring lead in the Calcium Product as

set forth in paragraph 23 below For those Calcium Products

where the recommended or maximum daily dose supplies more than

1500 milligrams of calcium a Settling Defendant shall provide a

I warning unless the Settling Defendant can show pursuant to

paragraph 210 and the testing protocol set forth in attached

i Exhibit A that the recommended daily dose of the Calcium Product

causes a total daily exposure to lead equal to or less than that

set forth in paragraph 24 below

23 A Settling Defendant shall be entitled to exclude from

the calculation of the daily lead exposure caused by a Calcium

Product the amount of lead per 1000 milligrams of calcium as set

forth in Table 23 of this paragraph 23 Compliance with this

Permanent Injunction is established and no warning is required

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 5

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under Proposition 65 where the lead exposure caused by an amount

of the Calcium Product supplying 1000 milligrams of calcium does

d not exceed the sum of (a) 05 micrograms of lead per thousand

milligrams of elemental calcium and (b) the amount of lead

excluded on the date of shipment as naturally occurring

pursuant to Table 23 of this paragraph 23 For purposes of

this Permanent Injunction Table 23 of this paragraph 23 sets

forth the amount of lead per 1000 milligrams of elemental calcium

which shall be deemed to be naturally occurring at the lowest

level currently feasible pursuant to Section 12501 of Title 22

cf the California Code of Regulations (CCR) The amounts of

lead and dates set forth in Table 23 shall apply as of the date

of shipment of the Calcium Product

TABLE 2 3

DATE NATURALLY OCCURRING AMOUNT OF LEAD PER 1000 MILLIGRAMS OF CALCIUM

July 1 1997 35 micrograms

April 1 1999 10 microgram

24 Even if no warning is required by paragraphs 22 and

23 above in the event that the recommended daily dose of any

Calcium Product as specified on the label or in any other

package material exceeds 1500 milligrams a Settling Defendant

shall provide a warning pursuant to Propcsition 65 if the total

daily lead exposure from the Calcium Product based on the

recommended daily dose exceeds 150 of the level that would

require a warning pursuant to paragraphs 22 and 23 (based on a

an amount of the Calcium Product supplying 1000 milligrams of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 6

23

27

1

2

3

4

5 J

6

7

8

9

10

11

12

J 8

2 1 1

2 5

27

calcium) above as of the date of shipment of the Calcium Product

For antacids that do not have a recommended daily dose for

purposes of this Permanent Injunction the term recommended

daily dose shall mean two-thirds of the maximum daily dose as

set forth on the label or in any other package material

25 For a Calcium Product that does not meet the standards

set forth in paragraphs 2 2 through 2 4 above a Settling

Defendant shall at the point of manufacture prior to shipment

to California or prior to distribution within California (1)

affix to or print on the Calcium Product container cap label or

unit package or (2) display at the point of sale of the Calcium

Product the following warning (the language in brackets in the

warning below is optional)

WARNING This product contains [lead] a chemical known [to the State of California] to cause birth defects or other reproductive harm

26 The warning required by paragraph 25 above shall be

prominently affixed to printed on or displayed proximately to

the point-of-sale of each Calcium Product with such

conspicuousness as compared with other words statements

designs or devices on the labeling as to render it likely to be

read and understood by an ordinary individual under customary

conditions of purchase or use If the warning is displayed on

the product container or labeling the warning shall be at least

the same size as the largest of any other health or safety

warnings on the product container or labeling and the word

warning 11 shall be in all capital letters and in bold print If

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 7

1

2

3

4

5

6

7

B

9

lO

11

12

14

1 5

19

20

21

22

23

24

25

26

27

printed on the labeling itself the warning shall be contained in

the same section of the labeling that states other safety

warnings concerning the use of the product The Attorney General

agrees to review any labeling or point of sale signs proposed to

be used under this section and advise the Settling Defendant as

to whether he believes such labeling or point of sale signs

comply with this section The requirement for product labeling

set forth herein is imposed pursuant to the terms of this

Permanent Injunction and is recognized by the parties as not

being the exclusive method of providing a warning under

Proposition 65 and its implementing regulations for the Calcium

Products

27 In the event that the Attorney General determines that

the naturally occurring levels set forth in Table 23 of

paragraph 23 above are higher than the lowest level currently

feasible as stated in 22 CCR section 12501 (a) (4) he shall have

the right to seek a modification of the Permanent Injunction to

reflect the alleged lowest level currently feasible of

naturally occurring lead in the Calcium Products Prior to

seeking such modification the Attorney General shall provide

written notice to the Settling Defendants that he intends to seek

the modification The parties shall have ninety (90) days in

which to confer with the Attorney General concerning the

modification If one or more of the Settling Defendants and the

Attorney General are unable to agree on a modification to the

Permanent Injunction the Attorney General may file a motion with

the court seeking a modification of the Permanent Injunction

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

I AMOUNT 8

1

2

3

4

5

6

7

B

9

10

11 1

12

13

14

l

16

17

18

19

2

2

2

23

24

25

26

2-1

In any motion by the Attorney General seeking such a

modification the burden of producing evidence shall be initially

upon the Attorney General to demonstrate a prima facie case that

the modification sought by the Attorney General is the lowest

level currently feasible The Settling Defendants who do not

agree to such modification retain the ultimate burden of proving

that the modification sought by the Attorney General is lower

than the lowest level currently feasible The parties hereby

agree that the Permanent Injunction should be modified to reflect

any agreement of the parties or any deterrrination by the Court

concerning what is the lowest level currently feasible for lead

in Calcium Products

28 In the event that Settling Defendants individually or

coilectively determine that the naturally occurring levels set

forth in Table 23 of paragraph 23 above are lower than the

lowest level currently feasible as stated in 22 CCR section

1250l(a) (4) such Settling Defendants shall have the right to

seek modification of the Permanent Injunction to reflect the

alleged lowest level currently feasible Prior to seeking such

modification such Settling Defendants shall provide written

notice to the Attorney General that they intend to seek the

modification The parties shall have ninety (90) days in which

to confer concerning the modification If the parties are unable

to agree on a modification to the Permanent Injunction such

Settling Defendants may file a motion with the Court seeking a

modification of the Permanent Injunction In any motion by

Settling Defendants seeking such modification the burden of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 9

1

1

2

3 Ii I

4 j

5 i I

6

7

8

9

10

11

12

L~

14

15

16

17

18

L 3

2J

21

22

23

24

25

26

27

producing evidence and of proof shall be on such Settling

Defendants to prove that the modification sought by the Settling

Defendants is the lowest level currently feasible The parties

hereby agree that the Permanent Injunction should be modified to

reflect any agreement of the parties or any determination by the

Court concerning what is the lowest level currently feasible

I for lead in Calcium Products

29 The term feasible as used in paragraphs 27 and 28

above includes but is not limited to a consideration of the

following factors availability and reliabilityof a supply of

low-lead calcium that meets the requirememts set forth in

paragraphs 22 23 and 24 above cost of low-lead calcium and

resulting increase in manufacturers prices resulting from the

use of the low-lead calcium performance characteristics of lowshy

lead calcium and of the resulting Calcium Product including but

middot not limited to formulation performance safety efficacy and

stability Nothing in this Permanent Injunction shall be

interpreted to require the Settling Defendants to use any calcium

material as an ingredient in a Calcium Product that would render

i their Calcium Product unlawful under state or federal law as

measured by existing andor future applicable California and

federal food and drug laws and regulations Nothing in this

Permanent Injunction shall be interpreted to preclude a Settling

Defendant from advocating for purposes of paragraphs 27 andor

28 that any proposed modification requiring a change in the type

of raw calcium source material as an ingredient in a Calcium

Product is not feasible as defined herein Nothing in this

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 10

ii

I

II I II

I

ii bullI

1

2

middot

4

c

E I

- ii

8

Permanent Injunction shall be interpreted to preclude the People

from advocating for purposes of paragraphs 2 7 andor 2 8 that

any proposed modification requiring a change in the type of raw

Calcium source material as an ingredient in a calcium product is

feasible as defined herein

9

1 c

1

I

1

I

IIIII

J~

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18

13

2J

21

22

23

~4

25

26

27

I

II

210 Each Settling Defendant shall maintain records

sufficient to establish its compliance with this Permanent

Injunction for a period of four years following the date of

shipment of any Calcium Product into California Such documents

shall be sufficient in detail to establish compliance with the

Protocol set forth in the attached Exhibit A Upon reasonable written notice from the Attorney Generals Office a Settling

Defendant must produce to the Attorney General within ten (10)

tusiness days of the receipt of the Attorney Generals notice

the documents required to be maintained according to this

paragraph To the extent that such documents contain information

which the Settling Defendant maintains is confidential

proprietary andor in the nature of a trade secret (or in fact a

trade secret) and upon written notice as to the asserted

confidential nature of this information by the Settling

Defendant the Attorney General agrees not to disclose this

information to third parties (though the Attorney General may

disclose this information to its attorneys and employees

including professional consultants provided that these persons

also agree to maintain the confidentiality of the information in

these documents) In addition any Settling Defendant may

designate as confidential trade secret information as that term

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 11

1

2

3

4

5

6

7

8

9

~c

2

l~

1 bull C _

~

20

21

22

23

24

25

26

27

is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

11

l

2

3

4

~

6

7

8

9

1

11

12

J3

l 4

17

l 3

~l

~6

shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

21

l

2

3

4

5

6

7

8

9

1G

11

2

3

14

JI

~7

s

~9

20

i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

22

23

24 [l

25 II I

26

2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

II al - Ii

I

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

l

2

3

4

E

7

8 1

9 1

c I

~l

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_

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21

22 1

Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

8

l

1 )

1L

l L

l

- C

8

bull =

)()

) I

22

23

24

25

26

27

i I

ii

for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

I

IIi

2 1111

31

4 I

) II 11

1~ 11 ii

7 fl

s II 1

g 1 I

l )

for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

middotJC-~ J 14~ LJ - ---lt__

Its S-~ LIL~~ Pr-ltt-S1J~L

Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

2

~ li

4

5 middot

E

E

C

the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

8

_ _

---

-

6

Its

Dated CONSAC

By

Its

APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

3

Dated

7

8

Dated 7997

l ) AP PROVED AS TO FORM

Dated

l -~

~ IS SO ORDERED

By

Its

NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

L c

2 l

2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

C

6

7

8

g

0

11

12

15

16

1 7

8

19

21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

lbull9116I 21 11Jl

I

Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

l-litl~ 4ll lUl

Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

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33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 13: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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21 Where required herein clear and reasonable warning

that use of Calcium Products exposes persons to lead a chemical

known to the State of California to cause birth defects or other

reproductive harm shall be provided by a Settling Defendant in

the manner provided in this Permanent Injunction

22 A Settling Defendant shall provide a warning pursuant

to paragraph 2 5 for each Calcium Product whose date of shipment

is on or after July 1 1997 unless the Settling Defendant can

show pursuant to paragraph 210 and the testing protocol set

forth in Exhibit A attached to this Permanent Injunction that

the Calcium Product causes a total daily exposure to lead of 05

micrograms or less based on the amount of the Calcium Product

supplying a thousand (1000) milligrams of elemental calcium

II excluding any naturally occurring lead in the Calcium Product as

set forth in paragraph 23 below For those Calcium Products

where the recommended or maximum daily dose supplies more than

1500 milligrams of calcium a Settling Defendant shall provide a

I warning unless the Settling Defendant can show pursuant to

paragraph 210 and the testing protocol set forth in attached

i Exhibit A that the recommended daily dose of the Calcium Product

causes a total daily exposure to lead equal to or less than that

set forth in paragraph 24 below

23 A Settling Defendant shall be entitled to exclude from

the calculation of the daily lead exposure caused by a Calcium

Product the amount of lead per 1000 milligrams of calcium as set

forth in Table 23 of this paragraph 23 Compliance with this

Permanent Injunction is established and no warning is required

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 5

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under Proposition 65 where the lead exposure caused by an amount

of the Calcium Product supplying 1000 milligrams of calcium does

d not exceed the sum of (a) 05 micrograms of lead per thousand

milligrams of elemental calcium and (b) the amount of lead

excluded on the date of shipment as naturally occurring

pursuant to Table 23 of this paragraph 23 For purposes of

this Permanent Injunction Table 23 of this paragraph 23 sets

forth the amount of lead per 1000 milligrams of elemental calcium

which shall be deemed to be naturally occurring at the lowest

level currently feasible pursuant to Section 12501 of Title 22

cf the California Code of Regulations (CCR) The amounts of

lead and dates set forth in Table 23 shall apply as of the date

of shipment of the Calcium Product

TABLE 2 3

DATE NATURALLY OCCURRING AMOUNT OF LEAD PER 1000 MILLIGRAMS OF CALCIUM

July 1 1997 35 micrograms

April 1 1999 10 microgram

24 Even if no warning is required by paragraphs 22 and

23 above in the event that the recommended daily dose of any

Calcium Product as specified on the label or in any other

package material exceeds 1500 milligrams a Settling Defendant

shall provide a warning pursuant to Propcsition 65 if the total

daily lead exposure from the Calcium Product based on the

recommended daily dose exceeds 150 of the level that would

require a warning pursuant to paragraphs 22 and 23 (based on a

an amount of the Calcium Product supplying 1000 milligrams of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 6

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calcium) above as of the date of shipment of the Calcium Product

For antacids that do not have a recommended daily dose for

purposes of this Permanent Injunction the term recommended

daily dose shall mean two-thirds of the maximum daily dose as

set forth on the label or in any other package material

25 For a Calcium Product that does not meet the standards

set forth in paragraphs 2 2 through 2 4 above a Settling

Defendant shall at the point of manufacture prior to shipment

to California or prior to distribution within California (1)

affix to or print on the Calcium Product container cap label or

unit package or (2) display at the point of sale of the Calcium

Product the following warning (the language in brackets in the

warning below is optional)

WARNING This product contains [lead] a chemical known [to the State of California] to cause birth defects or other reproductive harm

26 The warning required by paragraph 25 above shall be

prominently affixed to printed on or displayed proximately to

the point-of-sale of each Calcium Product with such

conspicuousness as compared with other words statements

designs or devices on the labeling as to render it likely to be

read and understood by an ordinary individual under customary

conditions of purchase or use If the warning is displayed on

the product container or labeling the warning shall be at least

the same size as the largest of any other health or safety

warnings on the product container or labeling and the word

warning 11 shall be in all capital letters and in bold print If

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 7

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printed on the labeling itself the warning shall be contained in

the same section of the labeling that states other safety

warnings concerning the use of the product The Attorney General

agrees to review any labeling or point of sale signs proposed to

be used under this section and advise the Settling Defendant as

to whether he believes such labeling or point of sale signs

comply with this section The requirement for product labeling

set forth herein is imposed pursuant to the terms of this

Permanent Injunction and is recognized by the parties as not

being the exclusive method of providing a warning under

Proposition 65 and its implementing regulations for the Calcium

Products

27 In the event that the Attorney General determines that

the naturally occurring levels set forth in Table 23 of

paragraph 23 above are higher than the lowest level currently

feasible as stated in 22 CCR section 12501 (a) (4) he shall have

the right to seek a modification of the Permanent Injunction to

reflect the alleged lowest level currently feasible of

naturally occurring lead in the Calcium Products Prior to

seeking such modification the Attorney General shall provide

written notice to the Settling Defendants that he intends to seek

the modification The parties shall have ninety (90) days in

which to confer with the Attorney General concerning the

modification If one or more of the Settling Defendants and the

Attorney General are unable to agree on a modification to the

Permanent Injunction the Attorney General may file a motion with

the court seeking a modification of the Permanent Injunction

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

I AMOUNT 8

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In any motion by the Attorney General seeking such a

modification the burden of producing evidence shall be initially

upon the Attorney General to demonstrate a prima facie case that

the modification sought by the Attorney General is the lowest

level currently feasible The Settling Defendants who do not

agree to such modification retain the ultimate burden of proving

that the modification sought by the Attorney General is lower

than the lowest level currently feasible The parties hereby

agree that the Permanent Injunction should be modified to reflect

any agreement of the parties or any deterrrination by the Court

concerning what is the lowest level currently feasible for lead

in Calcium Products

28 In the event that Settling Defendants individually or

coilectively determine that the naturally occurring levels set

forth in Table 23 of paragraph 23 above are lower than the

lowest level currently feasible as stated in 22 CCR section

1250l(a) (4) such Settling Defendants shall have the right to

seek modification of the Permanent Injunction to reflect the

alleged lowest level currently feasible Prior to seeking such

modification such Settling Defendants shall provide written

notice to the Attorney General that they intend to seek the

modification The parties shall have ninety (90) days in which

to confer concerning the modification If the parties are unable

to agree on a modification to the Permanent Injunction such

Settling Defendants may file a motion with the Court seeking a

modification of the Permanent Injunction In any motion by

Settling Defendants seeking such modification the burden of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 9

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producing evidence and of proof shall be on such Settling

Defendants to prove that the modification sought by the Settling

Defendants is the lowest level currently feasible The parties

hereby agree that the Permanent Injunction should be modified to

reflect any agreement of the parties or any determination by the

Court concerning what is the lowest level currently feasible

I for lead in Calcium Products

29 The term feasible as used in paragraphs 27 and 28

above includes but is not limited to a consideration of the

following factors availability and reliabilityof a supply of

low-lead calcium that meets the requirememts set forth in

paragraphs 22 23 and 24 above cost of low-lead calcium and

resulting increase in manufacturers prices resulting from the

use of the low-lead calcium performance characteristics of lowshy

lead calcium and of the resulting Calcium Product including but

middot not limited to formulation performance safety efficacy and

stability Nothing in this Permanent Injunction shall be

interpreted to require the Settling Defendants to use any calcium

material as an ingredient in a Calcium Product that would render

i their Calcium Product unlawful under state or federal law as

measured by existing andor future applicable California and

federal food and drug laws and regulations Nothing in this

Permanent Injunction shall be interpreted to preclude a Settling

Defendant from advocating for purposes of paragraphs 27 andor

28 that any proposed modification requiring a change in the type

of raw calcium source material as an ingredient in a Calcium

Product is not feasible as defined herein Nothing in this

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 10

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Permanent Injunction shall be interpreted to preclude the People

from advocating for purposes of paragraphs 2 7 andor 2 8 that

any proposed modification requiring a change in the type of raw

Calcium source material as an ingredient in a calcium product is

feasible as defined herein

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210 Each Settling Defendant shall maintain records

sufficient to establish its compliance with this Permanent

Injunction for a period of four years following the date of

shipment of any Calcium Product into California Such documents

shall be sufficient in detail to establish compliance with the

Protocol set forth in the attached Exhibit A Upon reasonable written notice from the Attorney Generals Office a Settling

Defendant must produce to the Attorney General within ten (10)

tusiness days of the receipt of the Attorney Generals notice

the documents required to be maintained according to this

paragraph To the extent that such documents contain information

which the Settling Defendant maintains is confidential

proprietary andor in the nature of a trade secret (or in fact a

trade secret) and upon written notice as to the asserted

confidential nature of this information by the Settling

Defendant the Attorney General agrees not to disclose this

information to third parties (though the Attorney General may

disclose this information to its attorneys and employees

including professional consultants provided that these persons

also agree to maintain the confidentiality of the information in

these documents) In addition any Settling Defendant may

designate as confidential trade secret information as that term

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 11

1

2

3

4

5

6

7

8

9

~c

2

l~

1 bull C _

~

20

21

22

23

24

25

26

27

is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

11

l

2

3

4

~

6

7

8

9

1

11

12

J3

l 4

17

l 3

~l

~6

shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

21

l

2

3

4

5

6

7

8

9

1G

11

2

3

14

JI

~7

s

~9

20

i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

22

23

24 [l

25 II I

26

2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

II al - Ii

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1

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

l

2

3

4

E

7

8 1

9 1

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21

22 1

Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

8

l

1 )

1L

l L

l

- C

8

bull =

)()

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22

23

24

25

26

27

i I

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for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

I

IIi

2 1111

31

4 I

) II 11

1~ 11 ii

7 fl

s II 1

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l )

for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

middotJC-~ J 14~ LJ - ---lt__

Its S-~ LIL~~ Pr-ltt-S1J~L

Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

2

~ li

4

5 middot

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E

C

the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

8

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---

-

6

Its

Dated CONSAC

By

Its

APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

3

Dated

7

8

Dated 7997

l ) AP PROVED AS TO FORM

Dated

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By

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NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

L c

2 l

2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

C

6

7

8

g

0

11

12

15

16

1 7

8

19

21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

lbull9116I 21 11Jl

I

Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

l-litl~ 4ll lUl

Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

l HI l 6l Vl l I IJ2

Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 14: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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26

under Proposition 65 where the lead exposure caused by an amount

of the Calcium Product supplying 1000 milligrams of calcium does

d not exceed the sum of (a) 05 micrograms of lead per thousand

milligrams of elemental calcium and (b) the amount of lead

excluded on the date of shipment as naturally occurring

pursuant to Table 23 of this paragraph 23 For purposes of

this Permanent Injunction Table 23 of this paragraph 23 sets

forth the amount of lead per 1000 milligrams of elemental calcium

which shall be deemed to be naturally occurring at the lowest

level currently feasible pursuant to Section 12501 of Title 22

cf the California Code of Regulations (CCR) The amounts of

lead and dates set forth in Table 23 shall apply as of the date

of shipment of the Calcium Product

TABLE 2 3

DATE NATURALLY OCCURRING AMOUNT OF LEAD PER 1000 MILLIGRAMS OF CALCIUM

July 1 1997 35 micrograms

April 1 1999 10 microgram

24 Even if no warning is required by paragraphs 22 and

23 above in the event that the recommended daily dose of any

Calcium Product as specified on the label or in any other

package material exceeds 1500 milligrams a Settling Defendant

shall provide a warning pursuant to Propcsition 65 if the total

daily lead exposure from the Calcium Product based on the

recommended daily dose exceeds 150 of the level that would

require a warning pursuant to paragraphs 22 and 23 (based on a

an amount of the Calcium Product supplying 1000 milligrams of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 6

23

27

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calcium) above as of the date of shipment of the Calcium Product

For antacids that do not have a recommended daily dose for

purposes of this Permanent Injunction the term recommended

daily dose shall mean two-thirds of the maximum daily dose as

set forth on the label or in any other package material

25 For a Calcium Product that does not meet the standards

set forth in paragraphs 2 2 through 2 4 above a Settling

Defendant shall at the point of manufacture prior to shipment

to California or prior to distribution within California (1)

affix to or print on the Calcium Product container cap label or

unit package or (2) display at the point of sale of the Calcium

Product the following warning (the language in brackets in the

warning below is optional)

WARNING This product contains [lead] a chemical known [to the State of California] to cause birth defects or other reproductive harm

26 The warning required by paragraph 25 above shall be

prominently affixed to printed on or displayed proximately to

the point-of-sale of each Calcium Product with such

conspicuousness as compared with other words statements

designs or devices on the labeling as to render it likely to be

read and understood by an ordinary individual under customary

conditions of purchase or use If the warning is displayed on

the product container or labeling the warning shall be at least

the same size as the largest of any other health or safety

warnings on the product container or labeling and the word

warning 11 shall be in all capital letters and in bold print If

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 7

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printed on the labeling itself the warning shall be contained in

the same section of the labeling that states other safety

warnings concerning the use of the product The Attorney General

agrees to review any labeling or point of sale signs proposed to

be used under this section and advise the Settling Defendant as

to whether he believes such labeling or point of sale signs

comply with this section The requirement for product labeling

set forth herein is imposed pursuant to the terms of this

Permanent Injunction and is recognized by the parties as not

being the exclusive method of providing a warning under

Proposition 65 and its implementing regulations for the Calcium

Products

27 In the event that the Attorney General determines that

the naturally occurring levels set forth in Table 23 of

paragraph 23 above are higher than the lowest level currently

feasible as stated in 22 CCR section 12501 (a) (4) he shall have

the right to seek a modification of the Permanent Injunction to

reflect the alleged lowest level currently feasible of

naturally occurring lead in the Calcium Products Prior to

seeking such modification the Attorney General shall provide

written notice to the Settling Defendants that he intends to seek

the modification The parties shall have ninety (90) days in

which to confer with the Attorney General concerning the

modification If one or more of the Settling Defendants and the

Attorney General are unable to agree on a modification to the

Permanent Injunction the Attorney General may file a motion with

the court seeking a modification of the Permanent Injunction

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

I AMOUNT 8

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16

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2

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In any motion by the Attorney General seeking such a

modification the burden of producing evidence shall be initially

upon the Attorney General to demonstrate a prima facie case that

the modification sought by the Attorney General is the lowest

level currently feasible The Settling Defendants who do not

agree to such modification retain the ultimate burden of proving

that the modification sought by the Attorney General is lower

than the lowest level currently feasible The parties hereby

agree that the Permanent Injunction should be modified to reflect

any agreement of the parties or any deterrrination by the Court

concerning what is the lowest level currently feasible for lead

in Calcium Products

28 In the event that Settling Defendants individually or

coilectively determine that the naturally occurring levels set

forth in Table 23 of paragraph 23 above are lower than the

lowest level currently feasible as stated in 22 CCR section

1250l(a) (4) such Settling Defendants shall have the right to

seek modification of the Permanent Injunction to reflect the

alleged lowest level currently feasible Prior to seeking such

modification such Settling Defendants shall provide written

notice to the Attorney General that they intend to seek the

modification The parties shall have ninety (90) days in which

to confer concerning the modification If the parties are unable

to agree on a modification to the Permanent Injunction such

Settling Defendants may file a motion with the Court seeking a

modification of the Permanent Injunction In any motion by

Settling Defendants seeking such modification the burden of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 9

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producing evidence and of proof shall be on such Settling

Defendants to prove that the modification sought by the Settling

Defendants is the lowest level currently feasible The parties

hereby agree that the Permanent Injunction should be modified to

reflect any agreement of the parties or any determination by the

Court concerning what is the lowest level currently feasible

I for lead in Calcium Products

29 The term feasible as used in paragraphs 27 and 28

above includes but is not limited to a consideration of the

following factors availability and reliabilityof a supply of

low-lead calcium that meets the requirememts set forth in

paragraphs 22 23 and 24 above cost of low-lead calcium and

resulting increase in manufacturers prices resulting from the

use of the low-lead calcium performance characteristics of lowshy

lead calcium and of the resulting Calcium Product including but

middot not limited to formulation performance safety efficacy and

stability Nothing in this Permanent Injunction shall be

interpreted to require the Settling Defendants to use any calcium

material as an ingredient in a Calcium Product that would render

i their Calcium Product unlawful under state or federal law as

measured by existing andor future applicable California and

federal food and drug laws and regulations Nothing in this

Permanent Injunction shall be interpreted to preclude a Settling

Defendant from advocating for purposes of paragraphs 27 andor

28 that any proposed modification requiring a change in the type

of raw calcium source material as an ingredient in a Calcium

Product is not feasible as defined herein Nothing in this

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 10

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Permanent Injunction shall be interpreted to preclude the People

from advocating for purposes of paragraphs 2 7 andor 2 8 that

any proposed modification requiring a change in the type of raw

Calcium source material as an ingredient in a calcium product is

feasible as defined herein

9

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210 Each Settling Defendant shall maintain records

sufficient to establish its compliance with this Permanent

Injunction for a period of four years following the date of

shipment of any Calcium Product into California Such documents

shall be sufficient in detail to establish compliance with the

Protocol set forth in the attached Exhibit A Upon reasonable written notice from the Attorney Generals Office a Settling

Defendant must produce to the Attorney General within ten (10)

tusiness days of the receipt of the Attorney Generals notice

the documents required to be maintained according to this

paragraph To the extent that such documents contain information

which the Settling Defendant maintains is confidential

proprietary andor in the nature of a trade secret (or in fact a

trade secret) and upon written notice as to the asserted

confidential nature of this information by the Settling

Defendant the Attorney General agrees not to disclose this

information to third parties (though the Attorney General may

disclose this information to its attorneys and employees

including professional consultants provided that these persons

also agree to maintain the confidentiality of the information in

these documents) In addition any Settling Defendant may

designate as confidential trade secret information as that term

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 11

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is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

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shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

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2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

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Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

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for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

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for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

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Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

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STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

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for Entry of Permanent Injunction is not entered by the Court

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the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

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DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

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Dated CONSAC

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APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

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STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

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NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

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Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

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Dated CONSAC

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APPROVED AS TO FORMDatedn 17 1997

By

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IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

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Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

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Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

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Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

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Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

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Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

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Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 15: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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calcium) above as of the date of shipment of the Calcium Product

For antacids that do not have a recommended daily dose for

purposes of this Permanent Injunction the term recommended

daily dose shall mean two-thirds of the maximum daily dose as

set forth on the label or in any other package material

25 For a Calcium Product that does not meet the standards

set forth in paragraphs 2 2 through 2 4 above a Settling

Defendant shall at the point of manufacture prior to shipment

to California or prior to distribution within California (1)

affix to or print on the Calcium Product container cap label or

unit package or (2) display at the point of sale of the Calcium

Product the following warning (the language in brackets in the

warning below is optional)

WARNING This product contains [lead] a chemical known [to the State of California] to cause birth defects or other reproductive harm

26 The warning required by paragraph 25 above shall be

prominently affixed to printed on or displayed proximately to

the point-of-sale of each Calcium Product with such

conspicuousness as compared with other words statements

designs or devices on the labeling as to render it likely to be

read and understood by an ordinary individual under customary

conditions of purchase or use If the warning is displayed on

the product container or labeling the warning shall be at least

the same size as the largest of any other health or safety

warnings on the product container or labeling and the word

warning 11 shall be in all capital letters and in bold print If

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 7

1

2

3

4

5

6

7

B

9

lO

11

12

14

1 5

19

20

21

22

23

24

25

26

27

printed on the labeling itself the warning shall be contained in

the same section of the labeling that states other safety

warnings concerning the use of the product The Attorney General

agrees to review any labeling or point of sale signs proposed to

be used under this section and advise the Settling Defendant as

to whether he believes such labeling or point of sale signs

comply with this section The requirement for product labeling

set forth herein is imposed pursuant to the terms of this

Permanent Injunction and is recognized by the parties as not

being the exclusive method of providing a warning under

Proposition 65 and its implementing regulations for the Calcium

Products

27 In the event that the Attorney General determines that

the naturally occurring levels set forth in Table 23 of

paragraph 23 above are higher than the lowest level currently

feasible as stated in 22 CCR section 12501 (a) (4) he shall have

the right to seek a modification of the Permanent Injunction to

reflect the alleged lowest level currently feasible of

naturally occurring lead in the Calcium Products Prior to

seeking such modification the Attorney General shall provide

written notice to the Settling Defendants that he intends to seek

the modification The parties shall have ninety (90) days in

which to confer with the Attorney General concerning the

modification If one or more of the Settling Defendants and the

Attorney General are unable to agree on a modification to the

Permanent Injunction the Attorney General may file a motion with

the court seeking a modification of the Permanent Injunction

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

I AMOUNT 8

1

2

3

4

5

6

7

B

9

10

11 1

12

13

14

l

16

17

18

19

2

2

2

23

24

25

26

2-1

In any motion by the Attorney General seeking such a

modification the burden of producing evidence shall be initially

upon the Attorney General to demonstrate a prima facie case that

the modification sought by the Attorney General is the lowest

level currently feasible The Settling Defendants who do not

agree to such modification retain the ultimate burden of proving

that the modification sought by the Attorney General is lower

than the lowest level currently feasible The parties hereby

agree that the Permanent Injunction should be modified to reflect

any agreement of the parties or any deterrrination by the Court

concerning what is the lowest level currently feasible for lead

in Calcium Products

28 In the event that Settling Defendants individually or

coilectively determine that the naturally occurring levels set

forth in Table 23 of paragraph 23 above are lower than the

lowest level currently feasible as stated in 22 CCR section

1250l(a) (4) such Settling Defendants shall have the right to

seek modification of the Permanent Injunction to reflect the

alleged lowest level currently feasible Prior to seeking such

modification such Settling Defendants shall provide written

notice to the Attorney General that they intend to seek the

modification The parties shall have ninety (90) days in which

to confer concerning the modification If the parties are unable

to agree on a modification to the Permanent Injunction such

Settling Defendants may file a motion with the Court seeking a

modification of the Permanent Injunction In any motion by

Settling Defendants seeking such modification the burden of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 9

1

1

2

3 Ii I

4 j

5 i I

6

7

8

9

10

11

12

L~

14

15

16

17

18

L 3

2J

21

22

23

24

25

26

27

producing evidence and of proof shall be on such Settling

Defendants to prove that the modification sought by the Settling

Defendants is the lowest level currently feasible The parties

hereby agree that the Permanent Injunction should be modified to

reflect any agreement of the parties or any determination by the

Court concerning what is the lowest level currently feasible

I for lead in Calcium Products

29 The term feasible as used in paragraphs 27 and 28

above includes but is not limited to a consideration of the

following factors availability and reliabilityof a supply of

low-lead calcium that meets the requirememts set forth in

paragraphs 22 23 and 24 above cost of low-lead calcium and

resulting increase in manufacturers prices resulting from the

use of the low-lead calcium performance characteristics of lowshy

lead calcium and of the resulting Calcium Product including but

middot not limited to formulation performance safety efficacy and

stability Nothing in this Permanent Injunction shall be

interpreted to require the Settling Defendants to use any calcium

material as an ingredient in a Calcium Product that would render

i their Calcium Product unlawful under state or federal law as

measured by existing andor future applicable California and

federal food and drug laws and regulations Nothing in this

Permanent Injunction shall be interpreted to preclude a Settling

Defendant from advocating for purposes of paragraphs 27 andor

28 that any proposed modification requiring a change in the type

of raw calcium source material as an ingredient in a Calcium

Product is not feasible as defined herein Nothing in this

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 10

ii

I

II I II

I

ii bullI

1

2

middot

4

c

E I

- ii

8

Permanent Injunction shall be interpreted to preclude the People

from advocating for purposes of paragraphs 2 7 andor 2 8 that

any proposed modification requiring a change in the type of raw

Calcium source material as an ingredient in a calcium product is

feasible as defined herein

9

1 c

1

I

1

I

IIIII

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18

13

2J

21

22

23

~4

25

26

27

I

II

210 Each Settling Defendant shall maintain records

sufficient to establish its compliance with this Permanent

Injunction for a period of four years following the date of

shipment of any Calcium Product into California Such documents

shall be sufficient in detail to establish compliance with the

Protocol set forth in the attached Exhibit A Upon reasonable written notice from the Attorney Generals Office a Settling

Defendant must produce to the Attorney General within ten (10)

tusiness days of the receipt of the Attorney Generals notice

the documents required to be maintained according to this

paragraph To the extent that such documents contain information

which the Settling Defendant maintains is confidential

proprietary andor in the nature of a trade secret (or in fact a

trade secret) and upon written notice as to the asserted

confidential nature of this information by the Settling

Defendant the Attorney General agrees not to disclose this

information to third parties (though the Attorney General may

disclose this information to its attorneys and employees

including professional consultants provided that these persons

also agree to maintain the confidentiality of the information in

these documents) In addition any Settling Defendant may

designate as confidential trade secret information as that term

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 11

1

2

3

4

5

6

7

8

9

~c

2

l~

1 bull C _

~

20

21

22

23

24

25

26

27

is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

11

l

2

3

4

~

6

7

8

9

1

11

12

J3

l 4

17

l 3

~l

~6

shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

21

l

2

3

4

5

6

7

8

9

1G

11

2

3

14

JI

~7

s

~9

20

i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

22

23

24 [l

25 II I

26

2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

II al - Ii

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

l

2

3

4

E

7

8 1

9 1

c I

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21

22 1

Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

8

l

1 )

1L

l L

l

- C

8

bull =

)()

) I

22

23

24

25

26

27

i I

ii

for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

I

IIi

2 1111

31

4 I

) II 11

1~ 11 ii

7 fl

s II 1

g 1 I

l )

for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

middotJC-~ J 14~ LJ - ---lt__

Its S-~ LIL~~ Pr-ltt-S1J~L

Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

2

~ li

4

5 middot

E

E

C

the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

8

_ _

---

-

6

Its

Dated CONSAC

By

Its

APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

3

Dated

7

8

Dated 7997

l ) AP PROVED AS TO FORM

Dated

l -~

~ IS SO ORDERED

By

Its

NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

L c

2 l

2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

C

6

7

8

g

0

11

12

15

16

1 7

8

19

21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

lbull9116I 21 11Jl

I

Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 16: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

1

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B

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27

printed on the labeling itself the warning shall be contained in

the same section of the labeling that states other safety

warnings concerning the use of the product The Attorney General

agrees to review any labeling or point of sale signs proposed to

be used under this section and advise the Settling Defendant as

to whether he believes such labeling or point of sale signs

comply with this section The requirement for product labeling

set forth herein is imposed pursuant to the terms of this

Permanent Injunction and is recognized by the parties as not

being the exclusive method of providing a warning under

Proposition 65 and its implementing regulations for the Calcium

Products

27 In the event that the Attorney General determines that

the naturally occurring levels set forth in Table 23 of

paragraph 23 above are higher than the lowest level currently

feasible as stated in 22 CCR section 12501 (a) (4) he shall have

the right to seek a modification of the Permanent Injunction to

reflect the alleged lowest level currently feasible of

naturally occurring lead in the Calcium Products Prior to

seeking such modification the Attorney General shall provide

written notice to the Settling Defendants that he intends to seek

the modification The parties shall have ninety (90) days in

which to confer with the Attorney General concerning the

modification If one or more of the Settling Defendants and the

Attorney General are unable to agree on a modification to the

Permanent Injunction the Attorney General may file a motion with

the court seeking a modification of the Permanent Injunction

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

I AMOUNT 8

1

2

3

4

5

6

7

B

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11 1

12

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2

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2-1

In any motion by the Attorney General seeking such a

modification the burden of producing evidence shall be initially

upon the Attorney General to demonstrate a prima facie case that

the modification sought by the Attorney General is the lowest

level currently feasible The Settling Defendants who do not

agree to such modification retain the ultimate burden of proving

that the modification sought by the Attorney General is lower

than the lowest level currently feasible The parties hereby

agree that the Permanent Injunction should be modified to reflect

any agreement of the parties or any deterrrination by the Court

concerning what is the lowest level currently feasible for lead

in Calcium Products

28 In the event that Settling Defendants individually or

coilectively determine that the naturally occurring levels set

forth in Table 23 of paragraph 23 above are lower than the

lowest level currently feasible as stated in 22 CCR section

1250l(a) (4) such Settling Defendants shall have the right to

seek modification of the Permanent Injunction to reflect the

alleged lowest level currently feasible Prior to seeking such

modification such Settling Defendants shall provide written

notice to the Attorney General that they intend to seek the

modification The parties shall have ninety (90) days in which

to confer concerning the modification If the parties are unable

to agree on a modification to the Permanent Injunction such

Settling Defendants may file a motion with the Court seeking a

modification of the Permanent Injunction In any motion by

Settling Defendants seeking such modification the burden of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 9

1

1

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3 Ii I

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producing evidence and of proof shall be on such Settling

Defendants to prove that the modification sought by the Settling

Defendants is the lowest level currently feasible The parties

hereby agree that the Permanent Injunction should be modified to

reflect any agreement of the parties or any determination by the

Court concerning what is the lowest level currently feasible

I for lead in Calcium Products

29 The term feasible as used in paragraphs 27 and 28

above includes but is not limited to a consideration of the

following factors availability and reliabilityof a supply of

low-lead calcium that meets the requirememts set forth in

paragraphs 22 23 and 24 above cost of low-lead calcium and

resulting increase in manufacturers prices resulting from the

use of the low-lead calcium performance characteristics of lowshy

lead calcium and of the resulting Calcium Product including but

middot not limited to formulation performance safety efficacy and

stability Nothing in this Permanent Injunction shall be

interpreted to require the Settling Defendants to use any calcium

material as an ingredient in a Calcium Product that would render

i their Calcium Product unlawful under state or federal law as

measured by existing andor future applicable California and

federal food and drug laws and regulations Nothing in this

Permanent Injunction shall be interpreted to preclude a Settling

Defendant from advocating for purposes of paragraphs 27 andor

28 that any proposed modification requiring a change in the type

of raw calcium source material as an ingredient in a Calcium

Product is not feasible as defined herein Nothing in this

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 10

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Permanent Injunction shall be interpreted to preclude the People

from advocating for purposes of paragraphs 2 7 andor 2 8 that

any proposed modification requiring a change in the type of raw

Calcium source material as an ingredient in a calcium product is

feasible as defined herein

9

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210 Each Settling Defendant shall maintain records

sufficient to establish its compliance with this Permanent

Injunction for a period of four years following the date of

shipment of any Calcium Product into California Such documents

shall be sufficient in detail to establish compliance with the

Protocol set forth in the attached Exhibit A Upon reasonable written notice from the Attorney Generals Office a Settling

Defendant must produce to the Attorney General within ten (10)

tusiness days of the receipt of the Attorney Generals notice

the documents required to be maintained according to this

paragraph To the extent that such documents contain information

which the Settling Defendant maintains is confidential

proprietary andor in the nature of a trade secret (or in fact a

trade secret) and upon written notice as to the asserted

confidential nature of this information by the Settling

Defendant the Attorney General agrees not to disclose this

information to third parties (though the Attorney General may

disclose this information to its attorneys and employees

including professional consultants provided that these persons

also agree to maintain the confidentiality of the information in

these documents) In addition any Settling Defendant may

designate as confidential trade secret information as that term

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 11

1

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27

is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

11

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2

3

4

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8

9

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shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

21

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2

3

4

5

6

7

8

9

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

22

23

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2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

l

2

3

4

E

7

8 1

9 1

c I

~l

~t

_

2)

21

22 1

Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

8

l

1 )

1L

l L

l

- C

8

bull =

)()

) I

22

23

24

25

26

27

i I

ii

for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

I

IIi

2 1111

31

4 I

) II 11

1~ 11 ii

7 fl

s II 1

g 1 I

l )

for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

middotJC-~ J 14~ LJ - ---lt__

Its S-~ LIL~~ Pr-ltt-S1J~L

Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

2

~ li

4

5 middot

E

E

C

the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

8

_ _

---

-

6

Its

Dated CONSAC

By

Its

APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

3

Dated

7

8

Dated 7997

l ) AP PROVED AS TO FORM

Dated

l -~

~ IS SO ORDERED

By

Its

NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

L c

2 l

2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

C

6

7

8

g

0

11

12

15

16

1 7

8

19

21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

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Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

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Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 17: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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2-1

In any motion by the Attorney General seeking such a

modification the burden of producing evidence shall be initially

upon the Attorney General to demonstrate a prima facie case that

the modification sought by the Attorney General is the lowest

level currently feasible The Settling Defendants who do not

agree to such modification retain the ultimate burden of proving

that the modification sought by the Attorney General is lower

than the lowest level currently feasible The parties hereby

agree that the Permanent Injunction should be modified to reflect

any agreement of the parties or any deterrrination by the Court

concerning what is the lowest level currently feasible for lead

in Calcium Products

28 In the event that Settling Defendants individually or

coilectively determine that the naturally occurring levels set

forth in Table 23 of paragraph 23 above are lower than the

lowest level currently feasible as stated in 22 CCR section

1250l(a) (4) such Settling Defendants shall have the right to

seek modification of the Permanent Injunction to reflect the

alleged lowest level currently feasible Prior to seeking such

modification such Settling Defendants shall provide written

notice to the Attorney General that they intend to seek the

modification The parties shall have ninety (90) days in which

to confer concerning the modification If the parties are unable

to agree on a modification to the Permanent Injunction such

Settling Defendants may file a motion with the Court seeking a

modification of the Permanent Injunction In any motion by

Settling Defendants seeking such modification the burden of

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 9

1

1

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producing evidence and of proof shall be on such Settling

Defendants to prove that the modification sought by the Settling

Defendants is the lowest level currently feasible The parties

hereby agree that the Permanent Injunction should be modified to

reflect any agreement of the parties or any determination by the

Court concerning what is the lowest level currently feasible

I for lead in Calcium Products

29 The term feasible as used in paragraphs 27 and 28

above includes but is not limited to a consideration of the

following factors availability and reliabilityof a supply of

low-lead calcium that meets the requirememts set forth in

paragraphs 22 23 and 24 above cost of low-lead calcium and

resulting increase in manufacturers prices resulting from the

use of the low-lead calcium performance characteristics of lowshy

lead calcium and of the resulting Calcium Product including but

middot not limited to formulation performance safety efficacy and

stability Nothing in this Permanent Injunction shall be

interpreted to require the Settling Defendants to use any calcium

material as an ingredient in a Calcium Product that would render

i their Calcium Product unlawful under state or federal law as

measured by existing andor future applicable California and

federal food and drug laws and regulations Nothing in this

Permanent Injunction shall be interpreted to preclude a Settling

Defendant from advocating for purposes of paragraphs 27 andor

28 that any proposed modification requiring a change in the type

of raw calcium source material as an ingredient in a Calcium

Product is not feasible as defined herein Nothing in this

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 10

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Permanent Injunction shall be interpreted to preclude the People

from advocating for purposes of paragraphs 2 7 andor 2 8 that

any proposed modification requiring a change in the type of raw

Calcium source material as an ingredient in a calcium product is

feasible as defined herein

9

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210 Each Settling Defendant shall maintain records

sufficient to establish its compliance with this Permanent

Injunction for a period of four years following the date of

shipment of any Calcium Product into California Such documents

shall be sufficient in detail to establish compliance with the

Protocol set forth in the attached Exhibit A Upon reasonable written notice from the Attorney Generals Office a Settling

Defendant must produce to the Attorney General within ten (10)

tusiness days of the receipt of the Attorney Generals notice

the documents required to be maintained according to this

paragraph To the extent that such documents contain information

which the Settling Defendant maintains is confidential

proprietary andor in the nature of a trade secret (or in fact a

trade secret) and upon written notice as to the asserted

confidential nature of this information by the Settling

Defendant the Attorney General agrees not to disclose this

information to third parties (though the Attorney General may

disclose this information to its attorneys and employees

including professional consultants provided that these persons

also agree to maintain the confidentiality of the information in

these documents) In addition any Settling Defendant may

designate as confidential trade secret information as that term

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 11

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is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

11

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2

3

4

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6

7

8

9

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shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

21

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4

5

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7

8

9

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14

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

22

23

24 [l

25 II I

26

2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

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Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

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for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

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2 1111

31

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for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

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Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

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the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

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Its

Dated CONSAC

By

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APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

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Dated

7

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Dated 7997

l ) AP PROVED AS TO FORM

Dated

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By

Its

NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

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6

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8

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0

11

12

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1 7

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19

21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

lbull9116I 21 11Jl

I

Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 18: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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producing evidence and of proof shall be on such Settling

Defendants to prove that the modification sought by the Settling

Defendants is the lowest level currently feasible The parties

hereby agree that the Permanent Injunction should be modified to

reflect any agreement of the parties or any determination by the

Court concerning what is the lowest level currently feasible

I for lead in Calcium Products

29 The term feasible as used in paragraphs 27 and 28

above includes but is not limited to a consideration of the

following factors availability and reliabilityof a supply of

low-lead calcium that meets the requirememts set forth in

paragraphs 22 23 and 24 above cost of low-lead calcium and

resulting increase in manufacturers prices resulting from the

use of the low-lead calcium performance characteristics of lowshy

lead calcium and of the resulting Calcium Product including but

middot not limited to formulation performance safety efficacy and

stability Nothing in this Permanent Injunction shall be

interpreted to require the Settling Defendants to use any calcium

material as an ingredient in a Calcium Product that would render

i their Calcium Product unlawful under state or federal law as

measured by existing andor future applicable California and

federal food and drug laws and regulations Nothing in this

Permanent Injunction shall be interpreted to preclude a Settling

Defendant from advocating for purposes of paragraphs 27 andor

28 that any proposed modification requiring a change in the type

of raw calcium source material as an ingredient in a Calcium

Product is not feasible as defined herein Nothing in this

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 10

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Permanent Injunction shall be interpreted to preclude the People

from advocating for purposes of paragraphs 2 7 andor 2 8 that

any proposed modification requiring a change in the type of raw

Calcium source material as an ingredient in a calcium product is

feasible as defined herein

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210 Each Settling Defendant shall maintain records

sufficient to establish its compliance with this Permanent

Injunction for a period of four years following the date of

shipment of any Calcium Product into California Such documents

shall be sufficient in detail to establish compliance with the

Protocol set forth in the attached Exhibit A Upon reasonable written notice from the Attorney Generals Office a Settling

Defendant must produce to the Attorney General within ten (10)

tusiness days of the receipt of the Attorney Generals notice

the documents required to be maintained according to this

paragraph To the extent that such documents contain information

which the Settling Defendant maintains is confidential

proprietary andor in the nature of a trade secret (or in fact a

trade secret) and upon written notice as to the asserted

confidential nature of this information by the Settling

Defendant the Attorney General agrees not to disclose this

information to third parties (though the Attorney General may

disclose this information to its attorneys and employees

including professional consultants provided that these persons

also agree to maintain the confidentiality of the information in

these documents) In addition any Settling Defendant may

designate as confidential trade secret information as that term

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 11

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is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

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shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

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2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

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Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

8

l

1 )

1L

l L

l

- C

8

bull =

)()

) I

22

23

24

25

26

27

i I

ii

for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

I

IIi

2 1111

31

4 I

) II 11

1~ 11 ii

7 fl

s II 1

g 1 I

l )

for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

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Its S-~ LIL~~ Pr-ltt-S1J~L

Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

2

~ li

4

5 middot

E

E

C

the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

8

_ _

---

-

6

Its

Dated CONSAC

By

Its

APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

3

Dated

7

8

Dated 7997

l ) AP PROVED AS TO FORM

Dated

l -~

~ IS SO ORDERED

By

Its

NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

L c

2 l

2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

C

6

7

8

g

0

11

12

15

16

1 7

8

19

21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

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Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

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Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 19: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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Permanent Injunction shall be interpreted to preclude the People

from advocating for purposes of paragraphs 2 7 andor 2 8 that

any proposed modification requiring a change in the type of raw

Calcium source material as an ingredient in a calcium product is

feasible as defined herein

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210 Each Settling Defendant shall maintain records

sufficient to establish its compliance with this Permanent

Injunction for a period of four years following the date of

shipment of any Calcium Product into California Such documents

shall be sufficient in detail to establish compliance with the

Protocol set forth in the attached Exhibit A Upon reasonable written notice from the Attorney Generals Office a Settling

Defendant must produce to the Attorney General within ten (10)

tusiness days of the receipt of the Attorney Generals notice

the documents required to be maintained according to this

paragraph To the extent that such documents contain information

which the Settling Defendant maintains is confidential

proprietary andor in the nature of a trade secret (or in fact a

trade secret) and upon written notice as to the asserted

confidential nature of this information by the Settling

Defendant the Attorney General agrees not to disclose this

information to third parties (though the Attorney General may

disclose this information to its attorneys and employees

including professional consultants provided that these persons

also agree to maintain the confidentiality of the information in

these documents) In addition any Settling Defendant may

designate as confidential trade secret information as that term

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 11

1

2

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7

8

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is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

11

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3

4

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7

8

9

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shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

21

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7

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

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2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

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Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

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for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

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31

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for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

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Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

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the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

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Its

Dated CONSAC

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APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

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Dated

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Dated

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By

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NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

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11

12

15

16

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Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

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Dated CONSAC

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APPROVED AS TO FORMDatedn 17 1997

By

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IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

lbull9116I 21 11Jl

I

Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 20: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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is defined in California Government Code section 62547 any data

provided to the Attorney Generals Office pursuant to this

paragraph or any other provision of this Permanent Injunction or

relating to the subject matter hereof and such information shall

not be released to any member of the public Provided however

that nothing in this provision shall prohibit the Attorney

General from disclosing information andor data designated as

confidential proprietary andor trade secret to other government

agencies as is necessary in pursuit of his enforcement authority

Furthermore nothing in this provision shall prohibit the

Attorney General from applying to the Court for a ruling

determining that the information andor data designated by a

bull Settling Defendant as confidential proprietary andor trade

secret should not be so designated and may be freely disclosed

3 Settlement Payments

31 Within thirty (30) days of execution of this Permanent

I Injunction as full final and complete satisfaction of all

claims for civil penalties or restitution for the alleged

violations up to and including July 1 1997 as set forth in

paragraph 101 for Calcium Supplements and Antacids Settling

Defendants shall pay the sum of $395500 to the Public Health

Trust a program of the California Public Health Foundation to be

used for research investigation and public education projects

approved by the Attorney General and relating to exposure to lead

in pregnancy andor nutritional factors related to lead exposure

among children Payment shall be made by delivery of certified

i funds payable to the Public Health Trust Making these payments

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT

AMOUNT 12

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4

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shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

21

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

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2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

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Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

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for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

I

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2 1111

31

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for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

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Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

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STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

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the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

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Its

Dated CONSAC

By

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APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

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Dated

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Dated

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By

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NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

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Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

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Dated CONSAC

By

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APPROVED AS TO FORMDatedn 17 1997

By

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IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

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Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

lbull9116I 21 11Jl

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Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

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Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

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23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

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24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

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Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

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Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

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Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 21: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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shall not be construed as an admission by Settling Defendants of

any fact issue of law or violation of law nor shall compliance

with the Permanent Injunction constitute or be construed as an

admission by suchSettling Defendants of any fact issue of law

or violation of law

4 Payment of Costs and Fees

41 Within thirty (30) days of execution of this Permanent

Injunction Settling Defendants shall pay $50000 as

reimbursement for the Attorney Generals costs of investigating

and prosecuting this action Payment shall be made by delivery

of certified funds payable to the Attorney General of the State

of California at 2101 Webster Street 12th Floor Oakland

California 94612-3049 (Attn Susan S Fiering Deputy Attorney

General)

5 Additional Enforcement Actions Continuing Obligations

51 By entering into this Permanent Injunction the People

do not waive any right to take further enforcement actions on any

violations not covered by the Complaint Nothing in this

errnanent Injunction shall be construed as diminishing each

Settling Defendants continuing obligation to comply with

Proposition 65 or the Unfair Competition Act in its future

activities

6 Enforcement of Permanent Injunction

61 The People may by motion or order to show cause before

the Superior Court of San Francisco enforce the terms and

conditions contained in this Permanent Injunction In any action

brought by the People to enforce this Permanent Injunction the

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 13

21

l

2

3

4

5

6

7

8

9

1G

11

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3

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

22

23

24 [l

25 II I

26

2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

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Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

8

l

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l L

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8

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22

23

24

25

26

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for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

I

IIi

2 1111

31

4 I

) II 11

1~ 11 ii

7 fl

s II 1

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l )

for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

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Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

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STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

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the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

8

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6

Its

Dated CONSAC

By

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APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

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STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

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Dated

7

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Dated 7997

l ) AP PROVED AS TO FORM

Dated

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By

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NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

L c

2 l

2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

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6

7

8

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0

11

12

15

16

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21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

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Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

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Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

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Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 22: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

21

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 14

22

23

24 [l

25 II I

26

2 7

People may seek whatever fines costs penalties or remedies as

provided by law for failure to comply with the Permanent

Injunction Where said failure to comply constitutes future

violations of Proposition 65 or other laws independent of the

Permanent Injunction andor those alleged in the Complaint the

People are not limited to enforcement of this Permanent

Injunction but may seek in another action whatever fines costs

penalties or remedies are provided by law for failure to comply

with Proposition 65 or other laws In any such future action

the standards and protocol set forth in Section 2 above as they

may be modified from time to time pursuant to paragraphs 27 or

28 shall apply However the rights of the Settling Defendants

to defend themselves and their actions in law or equity shall not

be abrogated or reduced in any fashion by the terms of this

paragraph

7 Application of Permanent Injunction

71 The Permanent Injunction shall apply to be binding

upon and inure to the benefit of the parties their divisions

subdivisions subsidiaries and affiliates and the successors or

assigns of each of them

8 o Application of Testing Standarc and Protocol

81 The testing standard and protocol set forth in Exhibit

A attached to this Permanent Injunction are based on

determinations concerning the nature of the laboratory test used

and its relationship to actual and specific conditions of Calcium

Product use This Permanent Injunction including but not

1 irni ted to this standard and protocol is the product of

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

l

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8 1

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22 1

Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

8

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for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

I

IIi

2 1111

31

4 I

) II 11

1~ 11 ii

7 fl

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for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

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Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

2

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C

the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

8

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---

-

6

Its

Dated CONSAC

By

Its

APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

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Dated

7

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Dated 7997

l ) AP PROVED AS TO FORM

Dated

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~ IS SO ORDERED

By

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NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

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2 l

2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

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4

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6

7

8

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0

11

12

15

16

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Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

lbull9116I 21 11Jl

I

Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 23: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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negotiation and compromise and is accepted by the parties for

purposes of settling compromising and resolving issues disputed

in this action including future compliance by the Settling

)efendants with Section 2 of this Permanent Injunction and shall

1ot be used for any other purpose or in any other matter and

except for the purpose of determining future compliance with this

d Permanent Injunction shall not constitute an adoption or

employrnent of a method of analysis for a lasted chemical in a

specific medium as set forth in 22 CCR section 1290l(b)

9 Authority to Stipulate to Permanent Injunction

91 Each signatory to this Permanent Injunction certifies that he or she is fully authorized by the party he or she I

represents to enter into this Permanent Injunction on behalf of

the party represented and legally to bind that party

10 Claims Covered

101 This Permanent Injunction is a final and binding

resolution between the People and each Settling Defendant of any

and all alleged violations of Proposition 65 the Business and

Frofessions Code Sections 17200 et seg aConsumersandor the

Legal Remedies Act Civil Code section 1750 et seq up through

shy July 1 1997 arising from failure to warn of exposure to lead

from consumption of any Settling Defendants Calcium Supplements

andor Antacids or those of any corporate affiliate that was

committed by thenamed Settling Defendant or by any entity within

its respective chain of distribution including but not limited

to distributors wholesalers and retailers of any of the

Sett 1 ing Defendants Calcium Supplements andor Antacids This 1

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 15

l

2

3

4

E

7

8 1

9 1

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21

22 1

Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

8

l

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l L

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8

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22

23

24

25

26

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for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

I

IIi

2 1111

31

4 I

) II 11

1~ 11 ii

7 fl

s II 1

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for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

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Its S-~ LIL~~ Pr-ltt-S1J~L

Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

2

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4

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E

C

the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

8

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---

-

6

Its

Dated CONSAC

By

Its

APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

3

Dated

7

8

Dated 7997

l ) AP PROVED AS TO FORM

Dated

l -~

~ IS SO ORDERED

By

Its

NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

L c

2 l

2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

C

6

7

8

g

0

11

12

15

16

1 7

8

19

21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

lbull9116I 21 11Jl

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Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

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Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

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Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 24: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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22 1

Permanent Injunction does not resolve any issues concerning

Settling Defendants Multiple VitaminsMinerals as defined in

paragraph 1 2 (c) abovemiddot The list of past and current Calcium

Supplements and Antacids to be governed by this Permanent

Injunction is set forth as Exhibit B attached to this Permanent

Injunction All new Calcium Supplements and Antacids hereafter

introduced into the stream of commerce for distribution or sale

in California shall be governed by this Permanent Injunction

Nothing in this Permanent Injunction shall preclude one or more

Settling Defendants from establishing that any non-calcium

ingredient in a Calcium Product other than Calcium Supplements

and Antacids contains naturally occurring lead at the lowest

level currently feasible pursuant to 22 CCR section 12501

11 Modification

111 This Permanent Injunction may be modified from time to

time by express written agreement of all Settling Defendants and

the Attorney General with the approval of the Court or by an

order of this Court

12 Execution in Counterparts

121 This Permanent Injunction may be executed in

counterparts which taken together shall be deemed to constitute

one and the same document

13 Entry of Stipulation for Entry of Permanent Injunction Required

131 This Stipulation for Entry of Permanent Injunction

shall be null and void and be without any force or effect

unless entered by the Court in this matter If the Stipulation

24

25

26

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 16

8

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22

23

24

25

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for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

I

IIi

2 1111

31

4 I

) II 11

1~ 11 ii

7 fl

s II 1

g 1 I

l )

for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

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Its S-~ LIL~~ Pr-ltt-S1J~L

Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

2

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4

5 middot

E

E

C

the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

8

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---

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6

Its

Dated CONSAC

By

Its

APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

3

Dated

7

8

Dated 7997

l ) AP PROVED AS TO FORM

Dated

l -~

~ IS SO ORDERED

By

Its

NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

L c

2 l

2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

C

6

7

8

g

0

11

12

15

16

1 7

8

19

21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

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Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

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Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

l-litl~ 4ll lUl

Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

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Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

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Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

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EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

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    • EXHIBIT A
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Page 25: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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for Entry of Permanent Injunction is not entered by the Court

the execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as_an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated 118 1997 DANIELE LUNGREN Attorneyt718 General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By JhSUSAN

Deputy Attorney Attorneys for the the State of California

Dated BAYER CORPORATION

By

Its

I Dated JOHNSON amp JOHNSONMERCK CONSUMER

PHARMACEUTICALS

By

Its

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION ANO PAYMENT OF SETTLEMENT AMOUNT 17

I

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2 1111

31

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for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

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Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

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STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

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the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

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violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

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Dated CONSAC

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APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

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STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

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Dated

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Dated 7997

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NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

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Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

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Dated CONSAC

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APPROVED AS TO FORMDatedn 17 1997

By

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IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

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Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

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Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

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Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

l-litl~ 4ll lUl

Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
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Page 26: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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for Entry of Permanent Injunction is not entered by the Court

1 1e execution of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

I admission by a Settling Defendant of any fact issue of law or violation of law

IT IS SO STIPULATED

Dated 1997 DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dat ed July 10 1997 BAYER CORPORATION

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Dated JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

By

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STIPULATION FOR ENTRY i OF PERMANENT INJUNCTION I AND PAYMENT OF SETTLEMENT

17bull AMOUNT

for Entry of Permanent Injunction is not entered by the Court

2

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E

C

the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

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6

Its

Dated CONSAC

By

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APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

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STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

3

Dated

7

8

Dated 7997

l ) AP PROVED AS TO FORM

Dated

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~ IS SO ORDERED

By

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NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

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2 l

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

C

6

7

8

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0

11

12

15

16

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21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

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APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

lbull9116I 21 11Jl

I

Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

l-litl~ 4ll lUl

Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

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Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 27: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

for Entry of Permanent Injunction is not entered by the Court

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C

the execucion of this Stipulation for Entry of Permanent

Injunction by any Settling Defendant shall not be construed as an

admission by a Settling Defendant of any fact issue of law or

violation of law

IT IS SO STIPULATED

Dated

bull C

DANIELE LUNGREN Attorney General of the State of California

RODERICK E WALSTON Chief Assistant Attorney General

THEODORA BERGER Assistant Attorney General

CRAIG C THOMPSON EDWARD G WEIL SUSAN S FIERING

Deputy Attorneys General

By SUSAN S FIERING

Deputy Attorney General Attorneys for the People of the State of California

Dated BAYER CORPORATION

By

Its

JOHNSON amp JOHNSONMERCK CONSUMER PHARMACEUTICALS

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 17

Dated OF AMWAY

By

4

8

_ _

---

-

6

Its

Dated CONSAC

By

Its

APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

) 4 )

STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

l

2

3

Dated

7

8

Dated 7997

l ) AP PROVED AS TO FORM

Dated

l -~

~ IS SO ORDERED

By

Its

NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

L c

2 l

2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

C

6

7

8

g

0

11

12

15

16

1 7

8

19

21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

Its

APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

lbull9116I 21 11Jl

I

Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

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Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

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Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

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EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
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Page 28: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

Dated OF AMWAY

By

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Dated CONSAC

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APPROVED AS TO FORM

Dated PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICK Esq

IT IS SO ORDERED

Dated JUL 2 4 1997 Judge Superior Court City and County of San Francisco

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STIPULATION FOR ENTRY I OF PERMANENT INJUNCTIONI AND PAYMENT OF SETTLEMENTIII AMOUNT 18

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STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

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2

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Dated

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Dated 7997

l ) AP PROVED AS TO FORM

Dated

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~ IS SO ORDERED

By

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NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

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2 l

2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

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4

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7

8

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0

11

12

15

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Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

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Dated CONSAC

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APPROVED AS TO FORMDatedn 17 1997

By

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IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

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Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

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Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

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Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

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Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

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Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

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EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

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    • EXHIBIT A
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Page 29: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

- 7

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

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2

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Dated

7

8

Dated 7997

l ) AP PROVED AS TO FORM

Dated

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~ IS SO ORDERED

By

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NUTRILITE A DIVISION OF AMWAY CORPORATION

CONSAC

PRESTON GATES amp ELLIS LLP

By ROGER LANE CARRICKEsq

Judge Superior Court l City and County of San Francisco

I

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2 4 i

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

1

2

3

4

C

6

7

8

g

0

11

12

15

16

1 7

8

19

21

Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

Its

Dated CONSAC

By

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APPROVED AS TO FORMDatedn 17 1997

By

LLP I

IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

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Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

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Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

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Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

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Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

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Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

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Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

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EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

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Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

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EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
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Page 30: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

STIPULATION FOR ENTRY OF PERMANENT INJUNCTION AND PAYMENT OF SETTLEMENT AMOUNT 18

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Dated NUTRILITE A DIVISION OF AMWAY CORPORPATION

By

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Dated CONSAC

By

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APPROVED AS TO FORMDatedn 17 1997

By

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IT IS SO ORDERED

Dated Judge Superior Court City and County of San Francisco

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

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Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

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Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

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Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

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Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

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Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

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Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

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EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 31: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

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Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

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Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

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Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

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Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

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Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

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Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

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Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

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Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

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Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 32: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

Callcium Containing Finished Product Lead Testing Protocol

Inductively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

49 I i6 ~ I l Jl

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

lbull9116I 21 11Jl

I

Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

l-litl~ 4ll lUl

Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

l HI l 6l Vl l I IJ2

Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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--~~~~--

EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 33: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

Pb 10 Protocol C 4Ctlve and Purpose

The purpose of this protocol is to define the procedures and methods used to analyze lead in calcium containing products The protocol defines the following requirements (1) method validation (2) sample collection amp retention (3) analyses of samples and (4) Limits This lead testing protocol defines the procedures limits and provides experimental confirmation that the data is reliable for the tested products This protocol shall become effective for purposes of establishing compliance with lead level limits only after all challenges to its contents and validity have been resolved or waived

The manufacturer shall be responsible for ensuring that all testing of calcium containing products whether performed by the manufacturers employees or by independent laboratories is performed properly All samples shall be obtained from either the production line or packaged product Sufficient quantities of product shall be obtained to perform the testing in duplicate at a minimum and to maintain bullretainbull samples sufficient in quantity for additional investigation Testing of a given formula of a calcium product shall be deemed to establish the lead level only for that formula of calcium product and formulas of calcium products which share all of the same ingredients (or a subset of the same ingredients but no additional ingredients) in substantially the same ratios as the tested calcium product Test results for a lot of a calcium product showing compliance on a lot-by-lot basis shall remain valid for purposes of demonstrating compliance for that lot of the calcium product Test results for a calcium product showing compliance on a product line basis shall remain valid for purposes of demonstrating product line compliance unless there is a material change in the products formula manufacturing process or ingredients For calcium products which are to be shipped on or after July 1 1997 the manufacturer must test such calcium products pursuant to this protocol by July 1 1997 or as soon thereafter as is reasonably feasible Manufacturers may rely on analytical testing which is substantially equivalent (ie bull results within 15 validation meeting the acceptance criteria for validation of this protocol and showing no assay bias to this protocol to demonstrate compliance for calcium products to be shipped on or after July 1 1997 until testing pursuant to this protocol is completed For calcium products which are to be shipped on or after April 1 1999 the manufacturer must test such calcium products pursuant to this protocol by April 1 1999 In the event of disagreement between testing results produced using a method complying with this protocol and testing results produced using a method which is not substantially equivalent to this protocol the former shall be preferred

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

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Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

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Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

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23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

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252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

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Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

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33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

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E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

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C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

l HI l 6l Vl l I IJ2

Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

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313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

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315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

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preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

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Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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bull ~ tmiddotf ~ ~ ltft~ -shy

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 34: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

Calcium Containing ied Product Lead Testing Protocol b1uuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGEmiddot3 OF 19

11 References

This lead testing protocol is designed to be used in combination with additional documentation included but are not limited to the following

a Instrument manuals b Instrument Software manuals c Standard Operating Procedures d Calibration Standard Certifications e Computerized System Qualification f Instrument Installation Qualification g instrument Operational Qualification h Instrument Performance Qualification

Analyst Training Records J USP 23 Section lt1225gt Validation of Compendia Methods pp 1982 to 1985

Category II Quantitative assays for impurities in bulk drug substances or degradation products in finished pharmaceutical products

k Federal Register Notice March 1 1995 International Conference on Harmonization (ICH) Guideline on Validation of Analytical Procedures Definitions and Terminology

i

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

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22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

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23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

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252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

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Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

l-litl~ 4ll lUl

Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

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33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

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E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

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C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

l HI l 6l Vl l I IJ2

Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

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313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

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314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

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315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

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preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

~ - bulll ~

bull

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middotmiddot ~ _ (

-bull ~ bull gti -middot ~1 4

bull ~ tmiddotf ~ ~ ltft~ -shy

_~lt shy middot-middot-~ -bull s

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middotmiddot t1middot middotshy

--~~~~--

EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 35: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

Calcium Containin[ _ ed Product Lead Testing Protocol Incuctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 4 OF 19

Pb 20 Method Vsldstlon Requirements

As detailed in this section the method shall be validated within any laboratory scheduled to conduct analyses of calcium containing products prior to conducting analyses intended to demonstrate compliance Validation of the method shall be repeated when and if significant changes in the laboratory (eg replreplacement of equipment) make reliance on the prior validation inappropriate

21 Accuracy

211 Definition

The accuracy of an analytical method expresses the closer1ess of test results obtained by that method to the true value Accuracy may often be expressed as percent recovery by the assay of known added amounts of analyte Accuracy is a measure of the exactness of the analytical method

212 Recovery Studies

The accuracy of the method should be assessed for the individual formulation tested The recovery studies should be performed in the range of 005 microgig to 300 microgig (ppm) on the representative finished product sample

A 05 microgml lead stock solution should be prepared by diluting 10 ml of 10 ppm lead standard solution with water to a total volume of 200 ml A minimum of sixteen samples should be prepared from a composite each having the sample weight defined in the procedure (1 gram) The first four samples are used to obtain the mean lead value (no lead addition) To the remaining samples add appropriate volumes of the lead stock solution to cover the recovery range of 005 microgig to 300microglg using a minimum of three concentrations with four samples per concentration levelmiddot

The theoretical amounts of lead In each sample is obtained by adding the average value obtained from the samples containing no spiked lead to the amount spiked in each of the three groups The microg of lead analyzed in each sample is divided by the theoretical calculated microg of lead amount and multiplied by 100 to obtain percent recovery

213 Accuracy Acceptance Criteria

The acceptance criteria for the spiked samples should be within 80 to 120 recovery

lbull9116I 21 11Jl

I

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22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

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23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

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PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

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252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

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Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

l-litl~ 4ll lUl

Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

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33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

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E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

l HI l 6l Vl l I IJ2

Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

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middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 36: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

Calcium Contalning ~ Product Lead Testing Protocol Ii tively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 5 OF 19

22 Precision amp Ruggedness

221 Definitions

1 Repeatability Repeatability expresses the precision under the same operation conditions over a short period of time

2 Intermediate Precision Intermediate precision expresses within-laboratory variation Different days (inter-day precision) different analysts different equipment different reagents acids and standards etc (Part of a ruggedness demonstration)

222 Precision Study (Repeatability)

Measure a prepared sample solution ten times and calculate the mean standard deviation and percent relative standard deviation (coefficient of variation)

223 Precision Study Acceptance Criteria

The percent relative standard deviation is less than 15

224 Ruggedness (Intermediate Precision) Study

Prepare a composite sample of at least 20 tablets or equivalent as defined in the method Have two different analysts analyze six samples each from the same composite sample on different days using different equipment (if possible) reagents standards and acids Calculate the mean standard deviation and relative standard deviatio11s separately for the two analysts data

225 Ruggedness Study Acceptance Criteria

Therelative standard deviations for each of the analysts are less than 25 The mean values between the two analysts are within 25 relative

49 i 16l 4121 I Ul

I

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

l-litl~ 4ll lUl

Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

l HI l 6l Vl l I IJ2

Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

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Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 37: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

Calcium Contalnlnr eel Product Lead Testing Protocol 1 dively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 6 OF 19

23 Limit of Detection

231 Definition

The limit of detection is a parameter of limit tests It is the lowest concentration of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions Thus limit tests merely substantiate that the analyte concentration is above or below a certain level The limit of detection is usually expressed as the concentration of analyte (eg percentage parts per billion etc in the sample

232 Instrumental Limit of Detection Studymiddot

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multiplied by 3 to give an estimate of the instrument signal at the limit of detection The limit of detection is subsequently validated by the analysis of three standards which will provide peak intensities at or near the signal level calculated for the limit of detection

233 Instrumental Limit of Detection Acceptance Criteria The instrumental limit of detection for lead should be 000110 ppm (microgmL or below

12bull91165 4121 lUl

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

l-litl~ 4ll lUl

Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

l HI l 6l Vl l I IJ2

Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

~ - bulll ~

bull

i bull ~

_~~-middot~middot

middotmiddot ~ _ (

-bull ~ bull gti -middot ~1 4

bull ~ tmiddotf ~ ~ ltft~ -shy

_~lt shy middot-middot-~ -bull s

_

~middot ~middot

_ middotshyshy _

-_middot

middotmiddot t1middot middotshy

--~~~~--

EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 38: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

Calcium Containlnp _Jed Product Lead Testing Protocol l ctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 7 OF 19

24 Limit of Quantitation

241 Definition

Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices such as impurities in bulk drug substances and degradation products in finished pharmaceuticals It is the lowest concentration analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions The limit of quantitation is expressed as the concentration of analyte (eg percent parts per billion etc) in the sample

242 Instrumental Limit of Quantitation Study

Six replicate measurements of the blank solution are made and the standard deviation of the baseline noise is calculated The standard deviation of the baseline noise is multip lied by 1 O to give an estimate of the instrument signal at the limit of quantitation The limit of quantitation is subsequently validated by the analysis of three standards

which will provide peak intensities at or near the signal calculated for the limit of quantitation

243 Instrumental Limit of Quantitatlon Acceptance Criteria The instrumental limit of quantitation for lead should be 0003 ppm (microgml) or below

25 Linearity and Range

251 Definitions

1 Linearity The linearity of the system is the ability to elicit test results that are directly or by amiddotwell-defined mathematical transformation proportional to the concentration of anafyte In samples within a given range Linearity is usually expressed in terms of the variance around the slope of the regression line calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte

2 Range The range of an analytical method is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with precision accuracy and linearity using the same units as test results (eg percent parts per million) obtained by the analytical method

middot1~116 4121 lU2

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

l-litl~ 4ll lUl

Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

l HI l 6l Vl l I IJ2

Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 39: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

Calcium Containing cl Product Lead Testing Protocol In ively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 8 OF 19

252 Linearity Study

Linearity check shall be performed using a minimum of eight different concentrations of a lead (Pb) standard solution and one or more internal standard solutions which will bracket the standard working range (from the limit of detection to 450 ppb) of the analysis The following stock standard solutions may be used in the linearity test Pb Ho Re Sc In Tl Bi and Tb If desired an additional linearity study may be conducted using a calcium containing solution shown to contain a lead solution concentration less than the method detection limit A linear regression plot and equation is calculated plotting the analyte concentration against response values

253 Linearity Acceptance Criteria

The response of the instrument is linear in the concentration range as demonstrated by a correlation coefficient (r2)of 098 or better

254 Range Data

Rar ge is established for each of the trace lead analysis test being validated by summarizing the accuracy Linearity and precision data

A result is invalid if it is above the validated range of the analytical method Values below 005 microgig should be reported as numbered estimates An acceptable range must include all specification limits for a method and expected results which may fall outside the specification level

255 Range Acceptance Criteria

The summarized data meets acceptance criteria defined in each section and demonstrates that samples within the concentration range of 005 microgig to 30 microgig (ppm) of lead can be analyzed by the analytical procedure

i

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

l-litl~ 4ll lUl

Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

l HI l 6l Vl l I IJ2

Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 40: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

Calcium Containing _1ed Product Lead Testing Protocol In---tlvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 9 OF 19

Pb 30 CPmiddotMS Finished Product Ssmpllng and Analytical Methodology

31 Scope

This method describes the sampling plan procedure data analysis and limits to be used to analyze calcium containing dosage forms for trace lead

Special Notes

bull All references in this protocol to the terms purified water or water shall mean ASTM Type I water

+ All glassware must be lead free and must be rinsed with 1 1 trace quality nitric acid and purified water followed by purified water followed by 1 1 hydrochloric acid and purified water followed again by purified water

bull All internal standards must be prepared from the same batch and contain the same amount of intemal standard reference material

bull Special precaution should be taken to avoid contamination bull Nitric acid may be substituted for hydrochloric acid if the acceptance criteria for

validation of this protocol continue to be met bull Sample preparation shall be appropriate for the dosage form being analyzed (eg gumgums which do not lend themselves to composite sample preparation) if the acceptance criteria for validation of this protocol continue to be met

32 Finished Product Sampling Plan

Special Notes

+ Sufficient sample of all products tested should be retained to permit additional testing at least in duplicate)

+ Random selection as used herein shall be pursuant to a scientifically and or regulatorily acceptable procedure

A For Lot-by-Lot compliance testing pursuant to Section 315 the samples used to prepare the composite shall be randomly selected from a given lot

B For Product Line compliance testing pursuant to Section 315 one sample shall be randomly selected from each of six different lots representative of the product to be shipped during the time period in question

l-litl~ 4ll lUl

Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

l HI l 6l Vl l I IJ2

Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

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bull

i bull ~

_~~-middot~middot

middotmiddot ~ _ (

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bull ~ tmiddotf ~ ~ ltft~ -shy

_~lt shy middot-middot-~ -bull s

_

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-_middot

middotmiddot t1middot middotshy

--~~~~--

EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 41: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

Calcium Coatainin[ oed Product Lead Testing Protocol IJ1wJctively Coupled Plasma Mass Spectrometry Procedure (lCP-MS)

PAGE 10 OF 19

33 Equipment bull Inductively Coupled Plasma Mass Spectrometer bull Analytical Balance bull Class A volumetric flasks or equivalent bull Class A Pipets or equivalent bull Sample grinding equipment bull Teflon Beakers or equivalent bull Heating Apparatus Hot plate or two stage microwave

34 Reagents bull Plasma Grade Lead Standards bull NIST Traceable bull Certified bull Purified Water bull Reference Control Sample NIST Bone Meal 1486 bull Plasma Grade Internal Standardsmiddot NIST Traceablemiddot Certified bull Trace Analysis grade Acids Ultrexreg or equivalent) Hydrochloric andor nitrlc

35 Preparation of Solutions Note Volumes may be increased proportionally

A Blank Solution

Prepare a solution of 1 HN03 1 HCI in water to be used in diluting standards and samples

B Stock Internal Standard Solution

Prepare a 1 O ppm internal standard solution using one or more of the standards listed in section 252

C Lead Stock Solution

Prepare a 1000 ppb lead stock solution by diluting reference material in 1 HN03 1 HCI

D Rinse Solution Containing 1 1 Trace Quality Nitric Acid and Water

Carefully add 100 ml of nitric acid to 100 ml of water

I bull91 65 421 1132

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

l HI l 6l Vl l I IJ2

Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

~ - bulll ~

bull

i bull ~

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middotmiddot ~ _ (

-bull ~ bull gti -middot ~1 4

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_ middotshyshy _

-_middot

middotmiddot t1middot middotshy

--~~~~--

EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 42: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

Calcium Containing ~ed Product Lead Testing Protocol Io Jvely Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 11 OF 19

E Rinse Solution Containing 1 1 Trace Quality Hydrochloric Acid and Water

Carefully add 100 ml of hydrochloric acid to 100 ml of water

36 Preparation of Standards

A Zero Level Standard Solution

Prepare a zero level standard (blank with 1 HN0 3 1 HCI solution and add the internal standard solution to obtair1 a level of 20 microI per 1 O ml

8 Standard Solutions of Lead

Prepare standard solutions in order to bracket the concentration range of the samples Matrix match standards and samples with 1 HN03 1 HCI solution and add the internal standard to obtain a level of 20 microI per 10 ml

37 Analytical Composite Sample

Weigh a minimum of 20 tablets (or equivalent) and determine the average tablet or equivalent) weight Grind the tablets to a fine uniform powder For non-tablet dosage forms an equivalent sample shall be prepared Proceed as directed under Sample Preparation Procedure

38 Instrument Sample Sequence

Prepare and analyze all samples In duplicate at a minimum

39 Sample Preparation Procedure

A Accurately weigh approximately 10 gram or a sample size appropriate to ensure that the result is in the validated range of the composite sample into a 250 ml teflon beaker (or equivalent)

B Add 8 mls of trace quality concentrated nitric acid to the beaker (enough to wet the sample

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

l HI l 6l Vl l I IJ2

Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

~ - bulll ~

bull

i bull ~

_~~-middot~middot

middotmiddot ~ _ (

-bull ~ bull gti -middot ~1 4

bull ~ tmiddotf ~ ~ ltft~ -shy

_~lt shy middot-middot-~ -bull s

_

~middot ~middot

_ middotshyshy _

-_middot

middotmiddot t1middot middotshy

--~~~~--

EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 43: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

Calcium Containi ashed Product Lead Testing Protocol 1nducdvely Coupled Plasma Mass Spectrometry Procedure ICP-MS)

PAGE 12 OF 19

C Allow the carbonate (if present) reaction to dissipate and swirl to mix or dissolve

D Cover with a lead-free watch glass or equivalent)

E Heat the sample using a hotplate or other heating technique such as a microwave digestion unit under a fume hood to aid digestion of the sample and if necessary reflux without boiling to dryness for a minimum of 10 to 15 minutes and for an additional time period as determined by the recovery studies if necessary to completely digest the sample If necessary to ensure complete digestion add an additional 5 ml of trace quality concentrated nitric acid to the sample during refluxing The need for this additional digestion must be demonstrated during the validation studies Remove from heat

F If necessary to ensure digestion of organic chemicals in the products that may interfere with the analysis a hydrogen peroxide reaction step may be added to the procedure In this case the product of Step E is further heated without boiling using a ribbed lead free watch glass until the solution evaporates to approximately 5 ml A covering solution over the bottom of the beaker must be maintained The sample is cooled and 2 ml of purified water and 3 ml of 30 hydrogen peroxide is added The beaker is covered with a lead free watch glass and warmed with a hot plate to start the peroxide reaction Care must be taken to ensure that losses do not occur due to excessively vigorous effervescence Heat until effervescence subsides and cool the beaker Continue to add 30 hydrogen peroxide in 1 ml aliquots with warming until the effervescence is minimal or until the general sample appearance is unchanged Do not add more than a total of 10 Oml hydrogen peroxide

G To either the solution from E of F depending upon whether the hydrogen peroxide reaction step was incorporated add either 3 ml of trace quality concentrated hydrochloric acid (to the solution from E) or 5 ml of trace quality concentrated hydrochloric acid (to the solution from F) If additional heating and reflux is required add 10 Oml of purified water Replace the watch glass and reflux without boiling to dryness For some products heating and reflux will not be necessary In that case the solution is swirled to mix and the reaction allowed to subside

H Cool by adding about 50 ml of purified water

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

l HI l 6l Vl l I IJ2

Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

~ - bulll ~

bull

i bull ~

_~~-middot~middot

middotmiddot ~ _ (

-bull ~ bull gti -middot ~1 4

bull ~ tmiddotf ~ ~ ltft~ -shy

_~lt shy middot-middot-~ -bull s

_

~middot ~middot

_ middotshyshy _

-_middot

middotmiddot t1middot middotshy

--~~~~--

EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 44: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

Calcium Containing ~ Product Lead Testing Protocol In vely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 13 OF 19

I Bring sample to a volume of 100 mls with purified water

J Particulates that might remain in the digestate should be removed by filtration (filter through Whatman No 41 filter paper or equivalent) centrifugation (2000 - 3000 rpm for 1 O minutes is usually sufficient) or by allowing the sample to settle

K Dilute sample for ICP-MS with 1 HN03 1 HCl diluent If the sample reading is outside the linear range dilute to bring the sample reading within the linear range but not below the limit of quantitation

L Add appropriate mLs of internal standard-eolution to match standards in order to obtain a level of 20 microI per 10 ml of final volume

M For each set of samples processed preparationmiddot blanks should be carried throughout the entire sample preparation and analytical process These blanks will be useful in determining if samples are being contaminated

31 O Reference Control Sample Procedure

A Accurately weigh an amount of the reference material which after dilution is expected to yield an amount of lead comparable to the amount of lead expected in the calcium finished product sample

8 Proceed as directed for steps 8 through L of Section 39

311 Instrument Calibration

Calibrate the instrument in order to bracket the concentration range of the prepared sample solutions Verify instrument calibration with midrange calibration cheeks

312 Instrument Conditions

Instrument must pass manufacturers specifications for resolution and sensitivity Read all isotopes for lead (206 207 208 amu) and report total lead as the sum of all three isotopes Read sample solution three times and average the intensities

l HI l 6l Vl l I IJ2

Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

~ - bulll ~

bull

i bull ~

_~~-middot~middot

middotmiddot ~ _ (

-bull ~ bull gti -middot ~1 4

bull ~ tmiddotf ~ ~ ltft~ -shy

_~lt shy middot-middot-~ -bull s

_

~middot ~middot

_ middotshyshy _

-_middot

middotmiddot t1middot middotshy

--~~~~--

EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 45: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

Calcium Contaln1ng ed Product Lead Testing Protocol dvely Coupled Plasma Mass Spectrometry t rocedure (ICP-MS)

PAGE 14 OF 19

313 Quality Control During Analysis

Initial QC Checks Include a reagent blank midrange calibration check second source midrange calibration check and spike If all data is acceptable the run can be accepted

Acceptance Criteria for lnltlal QC Checks Relative Limits Midrange Calibration Check 94 to 106 Second Source Midrange Calibration Check 93 to 107 Spike 80 to 120

Running QC Checks There should be a blank sample prep every ten samples spike sample every ten samples and a midrange calibration check every ten samples If all data is acceptable the data from the run can be reported If not a laboratory investigation will need to be conducted and specific corrective action put in place

Acceptance Criteria for Running QC Checks Relative Limits Midrange Calibration Check 94 to 106 Spike 80 to 120

Reference Sample For each run analyze either a standamiddotd reference material or a previously analyzed sample

Acceptance Criteria for Reference Sample isplusmn 20 of previous or certified value

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

~ - bulll ~

bull

i bull ~

_~~-middot~middot

middotmiddot ~ _ (

-bull ~ bull gti -middot ~1 4

bull ~ tmiddotf ~ ~ ltft~ -shy

_~lt shy middot-middot-~ -bull s

_

~middot ~middot

_ middotshyshy _

-_middot

middotmiddot t1middot middotshy

--~~~~--

EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 46: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

Calcium Containini JSbed Product Lead Testing Protocol lnauctively Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 15 OF 19

314 Sample Calculations

1 Micrograms of lead per gram (ppm)

microg Pbg = (C x DF)(g Sample wt x 1000)

Where C = Concentration of lead in ppb OF = Dilution Factor in ml Sample wt = sample weight in grams 1000 = Factor to convert from ppb to ppm

2 Micrograms of lead per unit dose

microg Pbunit dose = (microg Pbg)(g ave unit dose wt

Where g ave unit dose wt = Average unit dose weight in grams microg Pbg = ppm sample microg Pbunit dose = micrograms lead per unit dose

12bull116 VI IUl

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

~ - bulll ~

bull

i bull ~

_~~-middot~middot

middotmiddot ~ _ (

-bull ~ bull gti -middot ~1 4

bull ~ tmiddotf ~ ~ ltft~ -shy

_~lt shy middot-middot-~ -bull s

_

~middot ~middot

_ middotshyshy _

-_middot

middotmiddot t1middot middotshy

--~~~~--

EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 47: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

Calcium Containlo abed Product Lead Testing Protocol h-Jcdvely Coupled Plasma Mass Spectrometry Procedure (ICP-MS)

PAGE 16 OF 19

3 Micrograms of lead per gram of elemental calcium

microg Pbg Ca = (microg Pb per unit dose)(g Ca per unit dose)

Where

microg Pb per unit dose = micrograms of lead per unit dose Ca per unit dose = grams of elemental calcium per unit

dose microg Pbg Ca = micrograms of lead per gram of

elemental calcium

12~165 ltl21 liJ2

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

~ - bulll ~

bull

i bull ~

_~~-middot~middot

middotmiddot ~ _ (

-bull ~ bull gti -middot ~1 4

bull ~ tmiddotf ~ ~ ltft~ -shy

_~lt shy middot-middot-~ -bull s

_

~middot ~middot

_ middotshyshy _

-_middot

middotmiddot t1middot middotshy

--~~~~--

EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 48: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

Calcium Containing abed Product Lead Testing Protocol h tively Coupled Plasma Mass Spectrometry Procedure (ICPmiddotMS)

PAGE 17 OF 19

315 Comparison of Analytical Data to Sample Compliance Limit

The analytical data can establish that a given calcium product meets a given compliance limit for either (a) the product line by testing multiple lots of the calcium product or (b) for individual lots of the product line if six separate lots are not available for analysis if the results of the analysis of six lots does not establish product line compliance for that calcium product or if the manufacturer elects to establish compliance on a lot-by-lot rather than product line basis

A Product Line Compliance middot

Compliance is established for a product line if the resJlts of analyzing six samples selected pursuant to Section 32 produces a single tailed 90 upper confidence limit of the mean lead concentration based on the averages of the replicate analyses using a Students t-test or equivalent method which does not exceed the compliance limit If the mean does not exceed the compliance limit but the 90 confidence limit does analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that product line if the 90 confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other five lots) is obtained for a single lot then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded The basis for such confirmatory testing is to assure that the procedure (particularly sample preparation) was followed correctly

If product line compliance is not established as of a given point in time the manufacturer may undertake subsequent testing to establish product line compliance Un less and until product line compliance is established or as an alternative to establishing product line compliance lot-by-lot compliance may be established by the manufacturer

B Lot-By-Lot Compliance

An individual lot demonstrates compliance based on analysis of the composite sample selected pursuant to Section 32 if the average of the analytical replicates on that lot does not exceed the compliance limit and (a) for the first compliance phase no individual result may exceed the compliance limit and (b) for the second compliance phase no individual result may exceed 120 of the compliance limit If an individual lot does not demonstrate compliance pursuant to the immediately

ilbull9 ibl 4121 I Ul

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

~ - bulll ~

bull

i bull ~

_~~-middot~middot

middotmiddot ~ _ (

-bull ~ bull gti -middot ~1 4

bull ~ tmiddotf ~ ~ ltft~ -shy

_~lt shy middot-middot-~ -bull s

_

~middot ~middot

_ middotshyshy _

-_middot

middotmiddot t1middot middotshy

--~~~~--

EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 49: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

Calcium ContainiD ashed Product Lead Testing Protocol a-4amp1ctively Coupled Plasma Mass Spectrometry Procedure (ICPbullMS)

PAGE 18 OF 19

preceding sentence analysis of additional samples selected pursuant to Section 32 may be performed and compliance established for that lot if the single-tailed 90 upper confidence limit for the entire set of samples does not exceed the compliance limit If an unusual result (greater than 3 standard deviations from the mean of the other results) is obtained for a single result then confirmatory testing is required to verify correctness of the initial result In the event that the unusual result is more than 3 standard deviations from the mean of the other results after confirmatory testing the unusual result can be disregarded

lbull9 16l 4121 I 112

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

~ - bulll ~

bull

i bull ~

_~~-middot~middot

middotmiddot ~ _ (

-bull ~ bull gti -middot ~1 4

bull ~ tmiddotf ~ ~ ltft~ -shy

_~lt shy middot-middot-~ -bull s

_

~middot ~middot

_ middotshyshy _

-_middot

middotmiddot t1middot middotshy

--~~~~--

EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 50: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

middot Calcium Containing bed Product Lead Testina Protocol lno~~ively Coupled Plasma Mass Spectrometry Procedure (JCPmiddotMS)

PAGE 19 OF 19

Pb 40 Protocol Deviation

Document any deviations from the protocol with rational justification cause corrective action and any significance

~ - bulll ~

bull

i bull ~

_~~-middot~middot

middotmiddot ~ _ (

-bull ~ bull gti -middot ~1 4

bull ~ tmiddotf ~ ~ ltft~ -shy

_~lt shy middot-middot-~ -bull s

_

~middot ~middot

_ middotshyshy _

-_middot

middotmiddot t1middot middotshy

--~~~~--

EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 51: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

~ - bulll ~

bull

i bull ~

_~~-middot~middot

middotmiddot ~ _ (

-bull ~ bull gti -middot ~1 4

bull ~ tmiddotf ~ ~ ltft~ -shy

_~lt shy middot-middot-~ -bull s

_

~middot ~middot

_ middotshyshy _

-_middot

middotmiddot t1middot middotshy

--~~~~--

EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 52: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

EXBIBIT B LIS F CALCIUM SUPPLEMENTSAN ms

BAYER CORPORATION

Product Name One-A-Dayreg Calcium Plus Alka-Mintsreg Spearmint Flavor Allca-Mintsreg Cherry Flavor Alica-Mintsreg Assorted Flavors Alica-Mintsreg Tropical Flavor Alica-Seltzerreg Antacid Liquid Gelcaps Alica-Seltzerreg Caplets

CONSAC INDUSTRIES (COUNTRY LIFE)

Product Name Product Identification Cal Snack 2463 60 Cal Snack 2464 120 Target Mins Calcium Caps 2470 90 Target Mins Cal-Mag Caps 2476 90 Target Mins Cal-Mag Caps 2477 180 Target Mins Cal-Mag Complex 2480 90 Target Mins Cal-Mag Complex 2481 180 Target Mins Cal-Mag Potassium 2485 90 Target Mins Cal-Mag Potassium 2486 180 Target Mins Cal-Mag-Zinc 24$ 1 0 60 Target Mins Cal-Mag-Zinc 2491 120 Target Mins Nerve Osteo Support 2496 90 Nerve Osteo Support 2497 180 Target ~ Total Mins Complex 2510 60 Target Mins Total Mins Complex 25]1 120 Target Mins Total Mins Complex 2513 60 Target Mins Total Mins Complex 25]4 120 Maxi-Cal 2540 90 Maxi-Cal 2541 180 Cal-Mag Complex 25SO 90 Cal-Mag Complex 2551 180 Cal-Mag-Zinc 2601 100 Cal-Mag-Zinc 2604 250 Maxi-Mins Complex 2760 90 Maxi-Mins Complex 2761 180 Maxi Pre-Natal 8025 180

Product Identification

J JwOJOO I -0000 lDO-BSLTIXX t~07lnt97 llS3PM - 1- EXBIBITB

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 53: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

EXBlBITB LIST OF CALCIUM SUPPLEMENTSANTlhms

JORNSON amp JOHNSON bull MJi~RCK CONSUMER PHARMACEtinCALS

Product Name Mylanta Tablets Maximum Strength Mylanta Tablets Mylanta Gelcaps Antacid Childrens Mylanta Upset Stomach Relief

NUTRJLITE A DMSION OF AJwAY CORPORATION

Product Name troduct Idc-9tification Antacid Tablets DF-5582 Antacid Tablets DF-S525 Calcium Magnesium 600 mg NF-3022 Calcium Magnesium 600 mg NF-327$ Calcium 500 mg with Vitamin D SF-2390 Calcium 600 mg SF-2266 Calcium 600 mg SF-257t Calcium 600 mg SF-2625 Calcium 600 mg SF-2670 Calcium 600 mg SF-2864 Calcium 600 mg with Vitamin D SF-2391 Calcium 600 mg with Vitamin D SF-2631 Calcium 600 mg with Vitamin D SF-2827 Calcium 600 mg with Vitamin D SF-2867 Oyster Shell Calcium 250 mg SF-2250 Oyster Shell Calcium 250 mg SF-2251 Oyster Shell Calcium 250 mg SF-2252 Oyster Shell Calcium 2SO mg SF-2551

Product Identification

Jmiddotmiddot~121oo001poundXlmSLSTDOC Uwd Oitn97 ij3 Pt4 -2- EXHIBITB

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 54: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

EXHIBITB Lll JF CALCIUM SUPPLEMENTSAl ms

NUTRILITE A DMSION OF AMWAY CORPORATION (Continued)

Product Name Product ldendfication Oyster Shell Calcium 250 mg with with Vitamin D DF-5578

Oyster Shell Calcium 250 mg with with Vitamin D SF-2626

Oyster Shell Calcium 250 mg with with Vitamin D t SF-2865

Oyster Shell Calcium 500 mg SF-2500 Oyster Shell Calcium 500 mg SF-2501 Oyster Shell Calcium 500 mg SF-2502 Oyster Shell Calcium 500 mg SF-2627 Oyster Shell Calcium 500 mg SF-2866 Oyster Shell Calcium 500 mg with

VitaminD SF-2503 Oyster Shell Calcium 500 mg with

Vitamin D SF-25)4

~rrJOOJ6XIID~DOC gtiwd lJlDH7 1253 N -3- EXHIBIT H

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 55: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

EXHIBIT B

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its
Page 56: DANIELE. LUNGREN, Attorney General CRAIG C. THOMPSON ... · CRAIG C. THOMPSON Supervising Deputy Attorney General EDWARD G. WEIL SUSAN S. FIERING (State Bar No. 121621) Deputy Attorneys

EXHIBITB

MUL TIVITAMINMULTIMINERAL PROl)UCTS

Bugs Bunny Complete

Flintstones Complete

Flintstones Plus Calcium

One A Day Essential

One A Day Maximum

One A Day Mens Formula

One A Day 50 Plus

One A Day 55 Plus

One A Day Extra C Formula

One A Day Stressgard Formula

One A Day Within Womens Formula

One A Day Womens

DltXSSFI 2338491

  • Structure Bookmarks
    • EXHIBIT A
    • Its